GALT Database

  • Reference sequences were M96264.1 and cDNA M60091.1. cDNA number 1 is the "A" of the start codon.
  • Frameshift is documented by the original amino acid followed by the codon number and "fs" (ex. Leu159 fs).
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363 variants found

Genomic Position Location ▾ Mutation Type Nucleotide Change Protein Change Classification References Comments
Entire Gene Large Deletion Pathogenic Papachristoforou et. al. 2013
This large continuous deletion was the main mutation detected in Cyriot (Cyprus, Greece) patients presenting with classical galactosemia. This deletion spans 8489 bp and affects the entire GALT gene and non-translated regions of the adjacent gene coding for interleukin 11 receptor ( IL11RA). In addition to classic galactosemia, patients homozygous for this deletion presented with craniosynostosis (a phenotype associated with IL11RA gene defects), and one patient presented with microcephaly and optical atrophy. Two patients who were homozygous for this genotype had no GALT enzyme activity and a third had residual activity (5.9 micromol/h/g Hb). Three patients were heterozygous for this large deletion and p.K285N (neurological impact of galactosemia in these patients ranged from normal to severe learning disability as diagnosis and intervention was delayed).
5kb Gene Deletion 5kb del Pathogenic Berry (2001)
Break points defined by Muralidharan, ASHG 2005
5'UTR Gene Deletion 5.5kb del? Pathogenic Coffee (2006)
Common mutation in Ashkenasi Jewish Population. Must be considered carefully during molecular testing of this gene to avoid erroneous report of a single homozygous mutation (see publication for details on this deletion).
5'UTR c.-119_-116del Mild Kozak (1999)
Studies have shown this deletion affects promoter efficiency causing a 50% reduction of enzyme (25% reduction when only one allele is affected). This deletion was found in cis with p.N314D duarte variant and intronic polymorphisms c.378-27G>C, c.507+62G>A, and c.508-24G>A (referred to as the Duarte 2 haplotype). See Kozak 1999 for more information.
Exon 1 Missense c.2T>C p.M1T Pathogenic Crespo, C. et.al. 2015 Personal Communication
Argentinean patient was heterozygous for p.M1T and p.R148W. Enzyme activity was .
Exon 1 Missense c.1A>G p.M1V Pathogenic University of Bristol, unpublished
Exon 1 Deletion c.18delC? p.D7IfsX43 Pathogenic Zaffanello (2005)
Exon 1 Nonsense c.25C>T p.Q9X Pathogenic Gort (2009)
This nonsense mutation was reported in a Spanish galactosemic patient with p.I170N. This mutation causes early termination of the protein at codon 8 (codon 9 becomes the new stop codon).
Exon 1 Missense c.27G>C p.Q9H Pathogenic Item (2002)
Exon 1 Silent c.33C>T p.R11R Benign University of Bristol, unpublished
Exon 1 Indel c.41delinsTT p.A14delinsV Pathogenic University of Bristol, unpublished
Exon 1 Missense c.67A>G p.T23A Pathogenic Yang (2002)
Exon 1 Missense c.82G>A p.D28N Suspected Pathogenic University of Bristol, unpublished
Female presenting no clinical symptoms was heterozygous for the Duarte 2 mutations c.-119_-116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, c508-24G>A) and p.D28N. Enzyme activity was 5.5 µmol/h/Hgb (also reported low by outside lab).
Exon 1 Missense c.82G>C p.D28H Pathogenic Gort (2006)
This mutation was detected in a Spanish patient.
Exon 1 Missense c.82G>T p.D28Y Pathogenic Greber-Platzer (1997)
Exon 2 Missense c.90G>C p.Q30H Pathogenic O'Brien et al, unpublished
This mutation was detected with Q188R. Other laboratory results for this sample include IEF Pattern=GG; and enzyme activity= 0.5 ?mol/h/gHb.
Exon 2 Missense c.91C>A p.H31N Pathogenic University of Bristol, unpublished
Exon 2 Missense c.95T>A p.I32N Pathogenic Greber-Platzer (1997)
Exon 2 Missense c.98G>A p.R33H Pathogenic Gort (2006)
Detected in a Portuguese patient.
Exon 2 Missense c.98G>C p.R33P Pathogenic Viggiano et al. 2015
15yr-old italian patient was heterozygous for p.R33P and p.Q188R. Patient presented with liver failure, sepsis, and white matter anomalies. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 2 Missense c.100T>A p.Y34N Pathogenic Calderon et al, unpublished
p.Y34N heterozygous was detected in a father with enzyme level =16.4 ?mol/h/gHb. The child had both GALT enzyme activity and phenotype consistent with DG galactosemia (DNA results are not known); the mother was a Duarte variant carrier (N314D).
Exon 2 Missense c.100T>A p.Y34N Pathogenic Viggiano et al. 2015
Italian adult male was heterozygous for p.Y34N and p.Q188R. At diagnosis (newborn), patient presented with liver failure, sepsis, and cataracts. Outcome included cataracts, white matter anomalies, constructive apraxia, psychotic behavior, and anomalies of motor function. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 2 Missense c.107C>T p.P36L Pathogenic University of Bristol, unpublished
Exon 2 Missense c.110T>C p.L37P Likely pathogenic Calderon et al, unpublished
Caucasian female with abnormal NBS was heterozygous for p.L37P and p.Q344K. Clinical findings included vomiting and jaundice. Enzyme activity was 0.0 µmol/h/Hgb.
Exon 2 Missense c.113A>C p.Q38P Pathogenic Greber-Platzer (1997)
Exon 2 Silent c.117T>C p.D39D Benign University of Bristol, unpublished
Exon 2 Missense c.130G>A p.V44M Pathogenic Reichardt (1991)
Exon 2 Missense c.130G>T p.V44L Pathogenic Elsas (1998)
Exon 2 Missense c.131T>C p.V44A Pathogenic Calderon et al, unpublished
Female identified with abnormal NBS was heterozygous for p.V44A and the Duarte 2 haplotype. Enzyme activity was 4.7 ?mol/h/gHb and GAL-1-P was elevated.
Exon 2 Nonsense c.134_138del p.A46fs Pathogenic Item (2002)
Item et. al. (2002) reported this 5bp deletion as the only mutation in an Austrian patient selected during newborn screening. GALT activity suggested this patient to be a carrier of galactosemia. Cloning studies determined that this deletion causes a frameshift in the protein with A46 as the first affected amino acid. The new reading frame terminates at a stop codon at position 67.
Exon 2 Missense c.134C>T p.S45L Pathogenic Zekanowski (1999)
Exon 2 Missense c.152G>A p.R51Q Pathogenic Bosch (2005)
Exon 2 Missense c.152G>T p.R51L Pathogenic Tyfield (1999)
Exon 2 Nonsense c.160C>T p.Q54X Pathogenic University of Bristol, unpublished
Exon 2 Missense c.163G>T p.G55C Pathogenic Tyfield (1999)
Exon 2 Missense c.172G>A p.E58K Pathogenic Calderon et al, unpublished
Caucasian male identified with abnormal NBS and elevated GAL-1-P was heterozygous for p.E58K and p.Q188R. Enzyme activity was and patient was currently on lactose-free diet.
Exon 2 Missense c.184C>A p.L62M Benign Reichardt (1991)
Exon 2 Missense c.197C>A p.P66H Pathogenic Shin (2004)
Incorrectly reported asP66L in exon1
Exon 2 Missense c.197C>T p.P66L Pathogenic University of Bristol, unpublished
Exon 2 Missense c.199C>T p.R67C Pathogenic Sommer (1995)
Exon 2 Deletion c.207_214del p.D69_72Pdel Pathogenic University of Bristol, unpublished
Exon 2 Deletion c.220_221delCT p.L74fs (p.L74Pfs*18) Pathogenic Viggiano et al. 2015
Italian child (4 yrs-old), was heterozygous for p.L74fs and p.W134fs. At diagnosis, patient presented with liver failure, however, outcome at this time is normal. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 2 Insertion c.220_221insG p.L74fs Pathogenic Maceratesi (1996)
Exon 2 Missense c.221T>C p.L74P Pathogenic Reichardt (1992)
Exon 2 Missense c.227C>G p.P76R Uncertain Calderon et al, unpublished
Female with abnormal NBS was heterozygous for p.P76R, p.N314D, and c.-119_-116delGTCA.
Exon 2 Nonsense c.238C>T p.R80X Pathogenic Tyfield (1999)
Exon 2 Missense c.241G>A p.A81T Pathogenic Leslie (1992)
Exon 2 Missense c.247G>A p.G83R Pathogenic University of Bristol, unpublished
Exon 2 Missense c.248G>T p.G83V Pathogenic Viggiano et al. 2015
1 yr-old Italian male was heterozygous for p.G83V and p.W154X. Patient presented with liver failure and cataracts. Enzyme activity was less than 1 ?mol/h/gHb.
Intron 2 c.252+8T>C Suspected Benign Calderon et al, unpublished
Male with abnormal NBS was heterozygous for c.252+8T>C and p.Q188R. Patient did not have family history of Galactosemia and presented no clinical symptoms. Enzyme activity was detected at 7.34 µmol/h/Hgb.
Intron 2 c.253-11C>T Suspected Benign Calderon et al, unpublished
Caucasian male with abnormal NBS, presenting with vomitting, jaundice, and liver failure was heterozygous for c.253-11C>T. This variant is believed to be benign, however RNA studies were not performed.
Intron 2 Splice Site c.253-2A>G Pathogenic Yang (2002)
Found exclusively in hispanic patients (4 cases reported in the literature). Functional studies were not performed to determine its effects on the GALT enzyme. See publication. Also, male with abnormal NBS and high GAL-1-P was heterozygous for this splice variant and p.M336L.
Intron 2 Splice Site c.253-2A>G Pathogenic
Male identified with abnormal NBS was heterozygous for p.M336L and c.253-2A>G. Enzyme activity was 2 (repeated was 7-7.5 ?mol/h/gHb) and GAL-1-P was elevated. Mother and sister carried the c.253-2A>G variation. Asymptomatic Asian/Hispanic female on galactose-free diet was identified with abnormal NBS. Patient had persistant GAL-1-P elevation and was heterozygous for c.253-2A>G and the Duarte 2 haplotype.
Intron 2 c.253-2A>G Pathogenic
Hispanic female was heterozygous for c.253-2A>G and p.Q188R. Clinical findings included: lactose free diet, tremor/ataxia, developmental delay, mental retardation, delayed puberty, significant delayed myelination on brain MRI, high GAL-1P and low enzyme activity (outside lab). Family history included 2 cousins once removed.
Exon 3 Missense c.259C>A p.P87T Uncertain Calderon et al, unpublished
Female with abnormal NBS and enzyme activity of 13.6 µmol/h/Hgb was heterozygous for p.P87T.
Exon 3 Missense c.265T>C p.Y89H Pathogenic Ramandeep Singh et al, unpublished
Detected in an Indian patient presenting with decreased GALT activity, elevated blood galactose-1-phosphate levels, hepatosplenomegaly, jaundice, lethargy, failure to thrive, and sepsis. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 3 Missense c.265T>G p.Y89D Pathogenic University of Bristol, unpublished
Caucasian female with abnormal NBS was heterozygous for p.Y89D, and the Duarte 2 mutations c.-119_-116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, c508-24G>A). Patient was on a lactose free diet and had no family history of galactosemia. Enzyme activity was 4.3 µmol/h/Hgb.
Exon 3 Missense c.285T>G p.F95L Pathogenic University of Bristol, unpublished
Exon 3 Frameshift c.286_299delGACAACGACTTCCC p.D96Sfs*5 Pathogenic Choi et al 2014
Korean male child was heterozygous for this deletion and c.378-1G>C, presented with jaundice and cataracts. Enzyme activity was less than 0.1 ?mol/h/gHb. Patient was identified with abnormal newborn screening.
Exon 3 Frameshift c.286_299delGACAACGACTTCCC p.D96Sfs*5 Pathogenic Choi et al 2015
Korean female infant was heterozygous for this deletion and c.821-7A>G. Enzyme activity was 7.3 ?mol/h/gHb.
Exon 3 Missense c.290A>G p.N97S Pathogenic Ashino (1995)
Cryptic splice acceptor site (AG), 38bp del in exon 3 (nt 253-290). Results in shorter protein.
Exon 3 Missense c.290A>T p.N97I Suspected Pathogenic Calderon et al, unpublished
Male child diagnosed with galactosemia was heterozygous for p.N97I and p.L195P.
Exon 3 Missense c.292G>A p.D98N Pathogenic Tyfield (1999)
Newborn screen: Total Galactose >20 and GALT absent by immunoblot. Repeat Total galactose 17.3; GALT activity zero. On Soy, Gal-1-P level was 37.1 . Genotype homozygous. Normal development at 17 months. Submitted by mschneider@siumed.edu. Also, male patient tested in our laboratory had abnormal NBS and was heterozygous for this mutation and p.Q188R.
Exon 3 Missense c.292G>A p.D98N Pathogenic Calderon et al, unpublished
Female patient with abnormal NBS and high GALT1-P was heterozygous for p.D98N and p.Q188R. Enzyme activity was 3.6 ?mol/h/gHb. GALT-1-P was elevated even after 2 weeks of lactose free diet.
Exon 3 Missense c.292G>C p.D98H Pathogenic O'Brien et al, unpublished
This mutation was the only variation in this sample. Other laboratory results for this sample include IEF Pattern=GG; and enzyme activity= 0.9 ?mol/h/gHb.
Exon 3 Missense c.302C>A p.A101D Likely Pathogenic Choi et al 2014
Korean female infant was heterozygous for this variation and p.N314D. Enzyme activity was 6.2 ?mol/h/gHb. In silico analysis using Polyphen and SIFT suggested this variant to be pathogenic.
Exon 3 Missense c.308A>G p.Q103R Pathogenic Ramandeep Singh et al, unpublished
Detected in an Indian patient presenting with jaundice, hepatosplenomegaly, irritability, high colored urine, clay colored stools, progressive abdominal swelling, and decompensated cirrhosis with sepsis. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 3 Silent c.309G>A p.Q103Q Uncertain Ramandeep Singh et al, unpublished
Detected in an Indian patient. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Intron 3 Splice Site c.328+2T>C Pathogenic Gort (2009)
Found in a Spanish patient with Duarte 1 haplotype in the same allele and p.C180F in the other allele. This intronic mutation is thought to abolish the donor splice site by software prediction (not yet confirmed by cDNA studies).
Intron 3 c.328+29G>C Benign University of Bristol, unpublished
Intron 3 Splice Site c.329-2A>C Pathogenic Elsas (1995)
Intron 3 Splice Site c.329-1G>A Pathogenic Calderon et al, unpublished
Caucasian male with abnormal NBS was heterozygous for c.329-1G>A and the Duarte 2 haplotype. Enzyme activity was 5 ?mol/h/gHb and GAL-1-P was normal.
Exon 4 Silent c.330A>T p.G110G Benign University of Bristol, unpublished
Exon 4 Insertion c.333_334insA p.S112fs Pathogenic Tyfield (1999)
Exon 4 Missense c.336T>C p.S112R Pathogenic Velazquez-Aragon (2008)
This mutation was detected in a patient with no GALT enzyme activity. p.N314D was detected in the other allele.
Exon 4 Missense c.337G>A p.D113N Pathogenic Elsas (1998)
Exon 4 Missense c.341A>T p.H114L Pathogenic Elsas (1998)
Exon 4 Missense c.346C>A p.L116I Likely Pathogenic Ko et al. 2014
Korean male infant was heterozygous for this variant. Enzyme activity was 15.6 ?mol/h/gHb.
Exon 4 Missense c.350T>C p.F117S Pathogenic Elsas (1998)
Exon 4 Missense c.354A>C p.Q118H Pathogenic Elsas (1998)
Exon 4 Missense c.367C>G p.R123G Pathogenic Elsas (1998)
Exon 4 Missense c.368G>A p.R123Q Pathogenic Elsas (1998)
Exon 4 Missense c.374T>C p.V125A Pathogenic Elsas (1998)
Intron 4 Splice Site c.377+1G>T Pathogenic Hirokawa (1999)
Intron 4 Splice Site c.377+2T>A Mildly Pathogenic Calderon et al, unpublished
Asymptomatic caucasian male identified with abnormal NBS was heterozygous for c.377+2T>A and the Duarte 2 haplotype. Enzyme activity was 7.4 ?mol/h/gHb and GAL-1-P was elevated.
Intron 4 Splice Site c.377+2T>A Pathogenic Calderon et al. unpublished
Caucasian male identified with abnormal NBS had elevated GALT 1P (high) and GALT activity of 7.4 . This patient was heterozygous forc.377+2T>A the Duarte 2 haplotype (c.-119_-116del, p.N314D, c.378-27G>C, c.507+62G>A, c.508-24G>A)
Intron 4 c.377+53_ 1059
+87del
p.C126WfsX6 Pathogenic Gort (2006)
Published as p.K127_Q353delfsX5. Possible deletion of exons 5 to 10 and recombination between intron 4 and intron 10. This mutation was detected in a Spanish patient.
Intron 4 c.378-27G>C Benign
(Duarte 2)
Kozak (1999)
Found in cis with N314D duarte variant, c.-119_-116delGTCA and intronic polymorphisms c.507+62G>A,c.508-24G>A.
Intron 4 Splice Site c.378-1G>C Pathogenic Choi et al 2014
Korean male child was heterozygous for this splice site variant and c.286-299delGACAACGACTTCCC, presenting with jaundice and cataracts. Enzyme activity was less than 0.1 ?mol/h/gHb. Patient was identified with abnormal newborn screening.
Exon 5 Missense c.379A>G? p.K127E? Pathogenic Tyfield (1999)
Male patient presenting with GALT enzyme activity of 6.7umol/h/gHb had one copy of this mutation and one copy of the Duarte 2 haplotype.
Exon 5 Missense c.385A>T p.M129L Suspected Pathogenic Calderon et al, unpublished
Hispanic female with unknown NBS results and no family history of galactosemia was heterozygous for p.M129L. Patient presented no clinical symptoms.
Exon 5 Missense c.386T>C p.M129T Pathogenic Tyfield (1999)
Exon 5 Missense c.389G>A p.C130Y Pathogenic Elsas (1998)
Exon 5 Missense c.392T>G p.F131C Pathogenic University of Bristol, unpublished
Exon 5 Missense c.394C>T p.H132Y Pathogenic Elsas (1998)
Exon 5 Missense c.396C>A p.H132Q Pathogenic Calderon et al, unpublished
Identified in a patient with the Duarte 2 haplotype and GALT enzyme activity of 3.9 umol/h/gHb.
Exon 5 Frameshift c.398_399dupCC p.W134PfsX5 Pathogenic Calderon et al. unpublished
Caucasian male with abnormal NBS and absent GALT enzyme activity was heterozygous for both this mutation and p.Q188R.
Exon 5 Deletion c.400del p.W134fs Pathogenic Tyfield (1999)
Exon 5 Deletion c.400delT p.W134GfsX3 Pathogenic Viggiano et al. 2015
Female with abnormal NBS was heterozygous for c.400delT (p.W134fs) and Duarte 2 haplotype c.-119_-116delGTCA, p.N314D, c.378_27G>C, and c.508_24G>A. Patient's enzyme activity was 7.3 µmol/h/Hgb.
Exon 5 Missense c.404C>G p.S135W Pathogenic Bosch (2005)
Female with abnormal NBS was heterozygous for the Duarte 2 mutations c.-119_116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, c.508-24G>A) and p.S135W. Patient presented no clinical symptoms and enzyme activity was detected at 4.4 µmol/h/Hgb.
Exon 5 Missense c.404C>T p.S135L Pathogenic Reichardt (1992)
Function impact of this mutation can be found in Lai & Elsas 2001. Mol Genet Metab. 74(1-2):264-72; Christacos & Fridovich-Keil 2002. Mol Genet Metab.76(4):319-26. Impact of this mutation on galactose conversion was studied by Berry et al. 2000. Pediatr Res.48(3):323-8.
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
African-American female patient identified with abnormal NBS was heterozygous for p.F171S, S135L and the silent variants p.H315H and p.T292T. Enzyme activity was 1.7 ?mol/h/gHb.
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was 11.9?mol/h/gHb and GALT-1-P was mildly elevated.
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
African-American female patient identified with abnormal NBS was heterozygous for S135L and the silent variants p.H315H and p.T292T. Enzyme activity was 6.5 ?mol/h/gHb (tested in outside lab).
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was low (tested in outside lab) and GALT1-P was elevated.
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
Male with abnormal NBS was heterozygous for p.S293S and p.S135L. Enzyme activity was 10% of normal (tested in outside lab.) .
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
Male patient was heterozygous for c.508-17G>A and p.S135L.
Exon 5 Missense c.404C>T p.S135L Pathogenic Calderon et al, unpublished
African-American female identified with abnormal NBS was heterozygous for c.821-23dupT and p.S135L. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 5 Silent c.405G>A p.S135S Uncertain Calderon et al, unpublished
Female was heterozygous for p.S135S and p.Q188R.
Exon 5 Insertion c.410dupT? p.T138NfsX8 Pathogenic Bosch (2005)
Exon 5 Missense c.413C>T p.T138M Pathogenic Elsas (1995)
Caucasian female with abnormal NBS was heterozygous for p.S135L and p.T138M. Patient presented with no symptoms of galactosemia and had no family history. Additional case: Caucasian female with abnormal NBS was heterozygous for p.T138M and p.Q188R. This patient had low enzyme activity (outside lab) and no family history or clinical symptoms.
Exon 5 Missense c.413C>T p.T138M Pathogenic Calderon et al, unpublished
Caucasian male with abnormal NBS was heterozygous for p.T138M and p.N314D (Duarte 2 genotype). Enzyme activity was higher than expected for D/G (11.4 ?mol/h/gHb).
Exon 5 Missense c.416T>C p.L139P Pathogenic Leslie (1992)
Exon 5 Missense c.424A>G p.M142V Pathogenic Hirokawa (1999)
Exon 5 Missense c.425T>A p.M142K Pathogenic Reichardt (1991)
Caucasian male identified with abnormal NBS was heterozygous for p.M142K and p.L195P (tested in our laboratory). Enzyme activity was and GAL-1-P was high.
Exon 5 Missense c.425T>A p.M142L Pathogenic Calderon et al, unpublished
Female with abnormal NBS was heterozygous for p.Q188R and p.M142K. Enzyme activity was detected at 0 µmol/h/Hgb. Patient had a brother with same mutations.
Exon 5 Missense c.425T>C p.M142T Pathogenic Zaffanello (2005)
Exon 5 Missense c.425T>C p.M142T Pathogenic Viggiano et al. 2015
Italian child (1 yr-old) was heterozygous for p.M142T and p.Q188R. At diagnosis (newborn), patient had no symptoms of galactosemia and outcome at this time is normal. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 5 Missense c.428C>T p.S143L Pathogenic Greber-Platzer (1997)
Exon 5 Missense c.442C>G p.R148G Pathogenic Elsas (1998)
Exon 5 Missense c.442C>T p.R148W Pathogenic Reichardt (1992)
Caucasian/Middle Eastern female with abnormal NBS ws heterozygous for p.R148W and p.R231C. Enzyme activity was null and patient had no family history of galactosemia.
Exon 5 Missense c.443G>A p.R148Q Pathogenic Elsas (1995)
Exon 5 Missense c.448G>C p.V150L Pathogenic Maceratesi (1996)
Exon 5 Missense c.452T>C p.V151A Pathogenic Elsas (1995)
See also Fridovich-Keil et al. 1995. Am J Hum Genet. 56(3):640-6
Exon 5 Missense c.460T>C p.W154R Pathogenic University of Bristol, unpublished
Exon 5 Missense c.460T>G p.W154G Pathogenic Elsas (1995)
Exon 5 Nonsense c.462G>A p.W154X Pathogenic University of Bristol, unpublished
Exon 5 Nonsense c.462G>A p.W154X Pathogenic Viggiano et al. 2015
1 yr-old Italian male was heterozygous for p.G83V and p.W154X. Patient presented with liver failure and cataracts. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 5 Missense c.482T>C p.L161P Pathogenic University of Bristol, unpublished
Exon 5 Nonsense c.490C>T p.Q164X Pathogenic University of Bristol, unpublished
Exon 5 Missense c.493T>C p.Y165H Uncertain Choi et al 2014
Korean female infant was heterozygous for this variant and p.R333Q. Enzyme activity was 6.3 ?mol/h/gHb. In silico analysis of this variant using SIFT and Polyphen predicted this variant to be benign, however Human Splicing finder predicted this variant to cause activation of a cryptic splice site.
Exon 5 Silent c.495C>T p.Y165Y Benign University of Bristol, unpublished
Exon 5 Missense c.496C>G p.P166A Pathogenic Ramandeep Singh et al, unpublished
Detected in an Indian patient presenting with persistent jaundice, hepatosplenomegaly, pallor, high colored urine, clay colored stools, vomiting, altered sensorium, abdominal distension, and decreased GALT activity. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 5 Silent c.498T>C p.P166P Suspected Benign Calderon et al, unpublished
Adult female was heterozygous for p.P166P (c.498T>C). Patient was tested because she was an egg donor and intended father is a carrier for galactosemia.
Exon 5 Missense c.499T>C p.W167R Pathogenic Zekanowski (1999)
Exon 5 Missense c.502G>T p.V168L Pathogenic Calderon et al, unpublished
Philipino female patient presenting with bilirubinemia was homozygous for p.V168L. GALT enzyme activity was 0 umol/h/gHb.
Exon 5 Missense c.505C>A p.Q169K Pathogenic University of Bristol, unpublished
Intron 5 Splice Site c.507+2T>C Pathogenic Zekanowski (1999)
Intron 5 c.507+62G>A Benign
(Duarte 2)
Kozak (1999)
Found in cis with N314D duarte variant , c.-119_-116delGTCA and intronic polymorphisms c.378-27G>C,c.508-24G>A.
Intron 5 c.508-38T>C Benign University of Bristol, unpublished
Intron 5 c.508-29del Uncertain Bosch (2005)
Possible branch site mutation (see publication). Thought to delete 7 nts GGCTAAC from -26-32; branch point mutation but not confirmed on mRNA.
Intron 5 c.508-24G>A Benign
(Duarte 2)
Kozak (1999)
Found in cis with N314D duarte variant , c.-119_-116delGTCA and intronic polymorphisms c.378-27G>C, c.507+62G>A.
Intron 5 c.508-17G>A Benign Calderon et al, unpublished
Male patient was heterozygous for c.508-17G>A and p.S135L.
Intron 5 c.508-11C>A Benign Maceratesi (1996)
Intron 5 c.508-11C>G Benign Maceratesi (1996)
Intron 5 Splice Site c.508-5G>C Pathogenic Maceratesi (1996)
Exon 6 Missense c.509T>A p.I170N Pathogenic Gort (2009)
This mutation was reported in a Spanish galactosemic patient with p.Q9X.
Exon 6 Missense c.509T>C p.I170T Pathogenic Calderon et al, unpublished
Two siblings (non-identical twins) were each heterozygous for I170T and Q188R. Enzyme activity of either patient=0 umol/h/g Hgb.
Exon 6 Silent c.510C>T p.I170I Benign Item (2002)
Exon 6 Missense c.512T>C? p.F171S Pathogenic Reichardt (1992)
In our lab, an African American female with abnormal NBS was heterozygous for p.F171S and p.H315H. GAL-1P was reported high and enzyme activity was 9.4 µmol/h/Hgb.
Exon 6 Missense c.524G>A p.G175D Pathogenic University of Bristol, unpublished
Hispanic female with abnormal NBS was heterozygous for p.G175D and p.Q188R.
Exon 6 Insertion c.528_529insG p.M177fsX5 Pathogenic Maceratesi (1996)
Exon 6 Missense c.536G>A p.G179D Pathogenic Hirokawa (1999)
Exon 6 Missense c.539G>T p.C180F Pathogenic Gort (2009)
Found in a Spanish patient with Duarte 1 haplotype in the same allele and c.328+2T>C in the other allele.
Exon 6 Missense c.541T>G p.S181A Pathogenic Gort (2006)
This mutation was detected in a Spanish patient.
Exon 6 Missense c.542C>T p.S181F Pathogenic Ramandeep Singh et al, unpublished
Detected in an Indian patient presenting with cataracts, sepsis, persistent jaundice, hepatosplenomegaly, pallor, high colored urine, clay colored stools, abdominal distension and vomiting. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 6 Missense c.546C>A p.N182K Likely pathogenic Calderon et al, unpublished
African American male with abnormal NBS was heterozygous for the Duarte 2 mutations c.-119_-116delGTCA, p.N314D and p.N182K. Patient was placed on lactose free diet after birth, and enzyme activity was detected at 4.6 µmol/h/Hgb. Family history of Galactosemia is unknown.
Exon 6 Missense c.547C>A p.P183T Pathogenic Maceratesi (1996)
Exon 6 Missense c.550C>G p.H184D Pathogenic University of Bristol, unpublished
Exon 6 Missense c.552C>A p.H184Q Pathogenic Tyfield (1999)
Exon 6 Missense c.553C>T p.P185S Pathogenic Gort (2006)
Detected in a Portuguese patient.
Exon 6 Missense c.554C>A p.P185H Pathogenic Calderon (2007)
Compound heterozygous of P185H and R201C detected in a patient with erythrocyte GALT activity of 1.8 U/g Hgb
Exon 6 Missense c.554C>T p.P185L Pathogenic University of Bristol, unpublished
Exon 6 Missense c.556C>T p.H186Y Pathogenic University of Bristol, unpublished
In our lab, a Caucasian male with abnormal NBS and enzyme activity (outside lab) was heterozygous for p.H186Y and p.L195P. Patient was on a lactose free diet and presented with no symptoms of galactosemia.
Exon 6 Missense c.556C>A p.H186N Suspected Pathogenic Calderon et al, unpublished
Male with enzyme activity of 13.2 µmol/h/Hgb was heterozygous for p.H186N and c.*203C>T.
Exon 6 Missense c.563A>G p.Q188R Pathogenic Reichardt (1992)
Q188R is the most common mutation found in classical galactosemia. This mutation has been well described in the literature and was found to disrupt the active site and normal function of the GALT enzyme (Greeganage & Frey 1998. Biochemistry 37(41):14500-7; Lai et al. 1999. J Biol Chem 274(10):6559-66). Impact of this mutation on galactose conversion was studied by Berry et al. 2000. Pediatr Res.48(3):323-8.
Exon 6 Missense c.563A>G p.Q188R Pathogenic Calderon et al., unplublished
Caucasian male identified with abnormal NBS was heterozygous for p.L368P and p.Q188R. Enzyme activity was low (6.7 ?mol/h/gHb) and GAL-1-P was high.
Exon 6 Missense c.563A>G p.Q188R Pathogenic Calderon et al, unpublished
Male identified with abnormal NBS was heterozygous for p.E202K and p.Q188R. Enzyme activity was 0.3 ?mol/h/gHb and GAL-1-P was elevated.
Exon 6 Missense c.563A>G p.Q188R Pathogenic Calderon et al, unpublished
Caucasian female with abnormal NBS and having feeding problems was heterozygous for p.p.Q212X and p.Q188R. Enzyme activity was .
Exon 6 Missense c.563A>G p.Q188R Pathogenic Calderon et al, unpublished
Female child with enzyme activity was 0.8 ?mol/h/gHb and high GAL-1-P levels was heterozygous for p.W249X and p.Q188R.
Exon 6 Missense c.563A>G p.Q188R Pathogenic Calderon et al, unpublished
Caucasian male identified with abnormal NBS and elevated GAL-1-P was heterozygous for p.E58K and p.Q188R. Enzyme activity was and patient was currently on lactose-free diet.
Exon 6 Missense c.563A>C p.Q188P Pathogenic Tran et al 2015
6-yr old female was heterozygous for p.Q188P and p.Q188R. P.Q188P was shown to be a De Novo mutation since mother was the carrier for p.Q188R but father did not carry any mutations. Patient was identified with abnormal NBS and presented with poor feeding emesis, loose stools, jaundice, and elevated bilirubim levels. Enzyme activity is undetectable, but galactose-1-phosphate levels were 3.67mg% despite lactose free diet. Child has a history of speech delay and defect, seizures, and displayed white matter anomalies, and diffuse hypotonia upon 5-yr examination.
Intron 6 Splice Site c.564+1G>A Pathogenic University of Bristol, unpublished
Intron 6 c.564+7G>A Suspected Benign Calderon et al, unpublished
Male of Asian/Indian descent presenting with partial enzyme reduction was heterozygous for this variant and p.Q188R.
Intron 6 c.564+15G>A Benign University of Bristol, unpublished
Intron 6 c.564+32T>A Benign University of Bristol, unpublished
Intron 6 Splice Site c.565-2A>G Pathogenic University of Bristol, unpublished
Exon 7 Missense c.601C>A p.R201S Likely Pathogenic Crespo, C. et.al. Personal Communication
Argentinean patient was heterozygous for p.Q188R and p.R201S. Enzyme activity was and sibling with the same genotype presented with GALT activity of 1.1 µmol/h/gHb.
Exon 7 Missense c.574A>G p.S192G Pathogenic Gort (2006)
Detected in a Portuguese patient.
Exon 7 Missense c.575G>A p.S192N Pathogenic Elsas (1995)
Exon 7 Missense c.580T>C p.F194L Pathogenic Tyfield (1999)
Exon 7 Silent c.583C>T p.L195L Benign University of Bristol, unpublished
Exon 7 Missense c.584T>C p.L195P Pathogenic Reichardt (1992)
In our lab, a Caucasian male with abnormal NBS and enzyme activity (outside lab) was heterozygous for p.H186Y and p.L195P. Patient was on a lactose free diet and presented with no symptoms of galactosemia.
Exon 7 Missense c.586C>G p.P196A Uncertain Calderon et al, unpublished
Male was heterozygous for this mutation and p.Q188R.
Exon 7 Missense c.594T>G p.I198M Pathogenic Tyfield (1999)
Exon 7 Missense c.595G>A p.A199T Pathogenic Tyfield (1999)
Exon 7 Deletion c.598del p.Q200fs Pathogenic Elsas (1998)
Exon 7 Missense c.601C>T p.R201C Pathogenic Calderon (2007)
Compound heterozygous of R201C and P185H detected in a patient with erythrocyte GALT activity of 1.8 U/g Hgb
Exon 7 Missense c.602G>A p.R201H Pathogenic Elsas (1995)
Mutation is predicted to disrupt a hydrogen bond with Glu40 and impair enzyme stability. Patient enzyme activity was reported to be 1.6 U/gHb. This mutation was found together with p.Q188R. Patient was placed a galactose restricted diet following initial newborn screening. Patient is now an adult and has not presented developmental delays or other classical galactosemia associated signs.
Exon 7 Missense c.602G>A p.R201H Pathogenic Choi et al 2014
Korean female infant was heterozygous for this variation. Enzyme activity was 14.5 ?mol/h/gHb.
Exon 7 Missense c.604G>A p.E202K Pathogenic Calderon et al., unplublished
Male identified with abnormal NBS was heterozygous for p.E202K and p.Q188R. Enzyme activity was 0.3 ?mol/h/gHb and GAL-1-P was elevated.
Exon 7 Missense c.607G>A p.E203K Pathogenic Elsas (1995)
Another Incidence: detected in a female newborn with Q188R, both heterozygous. Baby was first identified with abnormal newborn screening but was not place on a diet until after 10 days. GALT enzyme level=0.2 mol/h/g Hgb. Baby was asymptomatic, possibly indicating that E203K may allow some enzyme to still be active other than in the blood (similar to S135L; see comments for this mutation).
Exon 7 Nonsense c.610C>T p.R204X Pathogenic Tyfield (1999)
This mutation was first reported in a Welsh patient (Tyfield et al. 1999) and later a Portuguese patient (Gort et al. 2006) with p.P265A and the Duarte 2 background in a single allele. Gort et al 2009 later reported another Portuguese patient with this mutation and p.Q188R. Our laboratory detected this mutation with p.P265A, the Duarte 2 variants, and p.Q188R in a patient with absent enzyme activity. p.R204X was also detected in an affected patient with p.K285N (separate chromosomes) with nearly no GALT activity (Chhay et al. 2007). Family members who were carriers had this mutation with p. T268N (a polymorphism). p.R204X was confirmed as a mutation affecting both expression and function of GALT in this same study.
Exon 7 Missense c.611G>C p.R204P Pathogenic Tyfield (1999)
Exon 7 Missense c.617A>G p.Q206R Suspected Pathogenic Calderon et al, unpublished
Male with reduced enzyme activity consitent with D/G variant galactosemia was heterozygous for this mutation, p.N314D and c.-119--116del GTCA.
Exon 7 Nonsense c.619C>T p.Q207X Pathogenic Yang (2002)
Exon 7 Missense c.626A>C p.Y209S Pathogenic Elsas (1998)
Exon 7 Missense c.626A>G p.Y209C Pathogenic Elsas (1998)
Caucasian female with abnormal NBS was heterozygous for p.Y209C and p.R333G. Enzyme activity was reported to be low (tested in outside laboratory).
Exon 7 Silent c.630G>A p.K210K Uncertain Ramandeep Singh et al, unpublished
Detected in an Indian patient. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 7 Nonsense c.634C>T p.Q212X Pathogenic Gathof (1995)
In our laboratory, a Caucasian female was identified having abnormal NBS and feeding problems. Patient was heterozygous for p.p.Q212X and p.Q188R and GALT enzyme activity was .
Exon 7 Missense c.635A>C p.Q212P Pathogenic O'Brien et al, unpublished
This mutation was detected with Q188R. Other laboratory results for this sample include IEF Pattern=GG; and enzyme activity= 1.2 umol/h/g Hgb
Exon 7 Missense c.640G>A p.G214R Uncertain Calderon et al, unpublished
Female was heterozygous for p.V151A and p.G214R.
Exon 7 Missense c.650T>C p.L217P Pathogenic Tyfield (1999)
Exon 7 Missense c.652C>G p.L218V Pathogenic O'Brien et al, unpublished
This mutation was found with N314D. Other laboratory results for this sample include IEF Pattern=DG; and enzyme activity= 4.1 umol/h/g Hgb
Exon 7 Silent c.652C>T p.L218L Benign
(Duarte 1)
Gathof (1995)
Found in cis with N314D (Duarte 1 or LA variant). This haplotype is associated with an increase in enzyme activity.
Exon 7 Deletion c.652del p.L218X Pathogenic Calderon (2007)
L218X heterozygous detected in a patient with erythrocyte GALT activity of 11.8 U/g Hgb
Exon 7 Insertion c.658dupG p.E220fsX17 Pathogenic Gort (2006)
This mutation was detected in a Spanish patient.
Exon 7 Missense c.658G>A p.E220K Pathogenic Calderon (2007)
E220K heterozygous detected in a patient with erythrocyte GALT activity of 11.2U/g Hgb
Exon 7 Missense c.666C>A p.S222R Likely Pathogenic Crespo, C. et.al. 2015 Personal Communication
Argentinean patient was heterozygous for p.Q188R and p.S222R. Enzyme activity was .
Exon 7 Missense c.667C>A p.R223S Pathogenic Calderon (2007)
Compound heterozygous of R223S and Q188R detected in a patient with erythrocyte GALT activity of 1.7 U/g Hgb
Exon 7 Missense c.676C>G p.L226V Pathogenic University of Bristol, unpublished
Exon 7 Missense c.677T>C p.L226P Pathogenic Elsas (1998)
Exon 7 Missense c.680T>C p.L227P Pathogenic Calderon el al, unpublished
Patient was heterozygous for this mutation and the Duarte 2 variant (5-UTR-119_-116delGTCA; p.N314D; and intronic polymorphisms c.378-27G>C, c.507+62G>A, c.508-24G>A). Enzyme activity=3.4 umol/h/g Hgb.
Exon 7 Missense c.687G>T p.K229N Pathogenic Bosch (2005)
Intron 7 Splice Site c.687+2T>C Pathogenic Tyfield (1999)
Exon 8 Missense c.688G>A p.E230K Uncertain Crespo, C. et.al. Personal Communication
Three unrelated Argentinean patients were heterozygous for p.Q188R and p.E230K. Enzyme activities were 5.5 and 2.3 µmol/h/g Hb. Enzyme activity was not available for the third patient.
Exon 8 Missense c.691C>T p.R231C Pathogenic University of Bristol, unpublished
Caucasian/Middle Eastern female with abnormal NBS ws heterozygous for p.R148W and p.R231C. Enzyme activity was null and patient had no family history of galactosemia.
Exon 8 Missense c.692G>A p.R231H Pathogenic Ashino (1995)
In our laboratory, a female patient was heterozygous for p.R231H and the Duarte 2 haplotype. Enzyme activity was 3.8 ?mol/h/gHb.
Exon 8 Missense c.692G>A p.R231H Pathogenic Calderon et al, unpublished
Caucasian male with abnormal NBS was heterozygous for p.R231H and p.P295T. Enzyme activity was .
Exon 8 Missense c.697G>C p.V233L Pathogenic Gort (2009)
Found in a Spanish galactosemic patient with c.253-2A>G.
Exon 8 Silent c.699C>A p.V233V Benign Maceratesi (1996)
Exon 8 Missense c.715T>C p.W239R Uncertain Calderon et al, unpublished
Male with abnormal NBS was heterozygous for p.W239R. NBS comfirmatory test was consistent with variant galactosemia.
Exon 8 Deletion c.719_728del10 p.L240SfsX25 Pathogenic Calderon et al, unpublished
This mutation was detected with the Duarte 2 variant (5-UTR-119_-116delGTCA; p.N314D; and intronic polymorphisms c.378-27G>C, c.507+62G>A, c.508-24G>A), both heterozygous. Patient was of hispanic/caucasian descent. GALT activity= 5.1. Patient was first identified with an abnormal newborn screen, however, no clinical symptons of galactosemia were reported.
Exon 8 Missense c.730C>T p.P244S Pathogenic Viggiano et al. 2015
Italian adult female was heterozygous for p.P244S and p. K285N. Patient presented with liver failure, sepsis, and cataracts at the time of diagnosis (birth). Patient outcome included cataracts, white matter anomalies, apraxia of speech. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 8 Missense c.745T>C p.W249R Pathogenic Tyfield (1999)
Exon 8 Nonsense c.747G>A p.W249X Pathogenic Hirokawa (1999)
Male with abnormal NBS was heterozygous for p.T249X and the Duarte 2 mutations c.-119_116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, c.508-24G>A). Patient was on a lactose free diet and had elevated GAL-1-P. Also, he received a blood transfusion two months after birth. No family history of galactosemia.
Exon 8 Missense c.748C>A p.P250T Pathogenic University of Bristol, unpublished
Caucasian male with abnormal NBS and no clinical symptoms was heterozygous for p.P250T. Patient had no family history of galactosemia and presented with enzyme activity of 11.3 µmol/h/Hgb.
Exon 8 Indel c.752_753delinsCT p.Y251S Pathogenic Calderon et al, unpublished
Caucasian female identified with abnormal NBS was heterozygous for c.752_753delinsCT and the Duarte 2 haplotype. Enzyme activity was 6.4 ?mol/h/gHb and GAL-1-P was elevated.
Exon 8 Missense c.752A>C? p.Y251S? Pathogenic Tyfield (1999)
Caucasian female patient presenting with jaundice and absent GALT enzyme activity was heterozygous for p.Y251S, p.Q188R, and a silent variant p.Y251Y (c.753C>T).
Exon 8 Missense c.752A>G p.Y251C Pathogenic Tyfield (1999)
Exon 8 Silent c.753C>T p.Y251Y Benign Calderon et al, unpublished
Caucasian female patient presenting with jaundice and absent GALT enzyme activity prensented with one copy of this silent variation, p.Q188R and p.Y251S.
Exon 8 Missense c.756G>T p.Q252H Pathogenic University of Bristol, unpublished
Exon 8 Silent c.759A>N p.T253T Benign Item (2002)
Exon 8 Insertion c.761insT? p.L255AfsX12 Pathogenic University of Bristol, unpublished
Exon 8 Deletion c.768_770del p.P257del Pathogenic Tyfield (1999)
See also Kozak et al 1999. Hum Mut 15(2):206
Exon 8 Missense c.769C>A p.P257T Pathogenic Choi et al 2014
Korean male infant was heterozygous for this variation. Enzyme activity was 11.6 ?mol/h/gHb. In silico analysis with Polyphen and SIFT indicate this variant is pathogenic.
Exon 8 Missense c.770C>T p.P257L Pathogenic Gort (2009)
Found in a Spanish galactosemic patient with p.L195P.
Exon 8 Missense c.772C>T p.R258C Pathogenic Elsas (1998)
Female was heterozygous for p.Q188R and p.R258C. Enzyme activity was detected at 0.4 µmol/h/Hgb.
Exon 8 Missense c.775C>T p.R259W Pathogenic Tyfield (1999)
Caucasian female patient with classical galactosemia (including jaundice, vomitting, diarrhea, liver failure, sepsis and speech problems) was heterozygous for this mutation and p.Q188R.
Exon 8 Missense c.775C>T p.R259W Pathogenic Calderon et al, unpublished
Asymptomatic Asian-Vietnamese female with abnormal NBS was heterozygous for p.R259W. Enzyme was reported to be low (tested in outside lab.).
Exon 8 Missense c.776G>A p.R259Q Pathogenic Calderon et al, unpublished
Compound heterozygous of R259Q and S135L detected in a patient with erythrocyte GALT activity of 0 ?mol/h/gHb.
Exon 8 Deletion c.778_789del p.H260_R263del Pathogenic Elsas (1998)
Exon 8 Missense c.785G>C p.R262P Pathogenic Elsas (1998)
Exon 8 Indel c.[790_792delC; 792_793insG] p.L264X Pathogenic Elsas (1998)
Found in a patient in our laboratory with a confirmed diagnosis of galactosemia. Patient was apparently homozygous for this mutation by sequencing, but unable to rule out the possibility of compound heterozygosity for this mutation and a large deletion. Given parent?s consanguineous relationship, proband may be a true homozygote.
Exon 8 Missense c.793C>G p.P265A Pathogenic Gort (2006)
This missense mutation was reported in a Welsh patient and later a Portuguese patient (Gort et al. 2006) with p.R204X and the Duarte 2 background in a single allele. Our laboratory detected this mutation with p.R204X, the Duarte 2 variants, and p.Q188R in a patient with absent enzyme activity.
Exon 8 Missense c.799C>G p.L267V Pathogenic Viggiano et al. 2015
Italian child (9 yr-old) was heterozygous for p.L267V and p.L267R. At time of diagnosis patient presented with liver failure. Patient outcome included apraxia of speech and white matter anomalies. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 8 Missense c.800T>G p.L267R Pathogenic Viggiano et al. 2015
Italian child (9 yr-old) was heterozygous for p.L267V and p.L267R. At time of diagnosis (newborn) patient presented with liver failure. Patient outcome included apraxia of speech and white matter anomalies. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 8 Missense c.803C>A p.T268N Benign Chhay et al, 2008
This variation was shown to be a polymorphism causing no impact on protein expression or function. Findings were consistent with clinical observations. See publication for further details.
Exon 8 Missense c.812A>G p.E271G Pathogenic University of Bristol, unpublished
Caucasian female with abnormal NBS was heterozygous for p.E271G and p.Q188R and p.I378V. Patient had no known family history of galactosemia and presented with jaundice, abnormal coagulations, and high Gal-1P. Enzyme activity was 0 µmol/h/Hgb.
Exon 8 Missense c.812G>C p.E271D Pathogenic Viggiano et al. 2015
Italian child (6 yr-old) was heterozygous for p.E271D and p.K285N. At the time of diagnosis (newborn), patient presented with liver failure and cataracts. Patient has a normal outcome at this stage. Enzyme activity was less than 1 ?mol/h/gHb.
Exon 8 Missense c.814C>G p.R272G Pathogenic Tyfield (1999)
Exon 8 Missense c.815G>A p.R272H Pathogenic O'Brien et al, unpublished
This mutation was found with Q188R. Other laboratory results for this sample include IEF Pattern=GG; and enzyme activity= 0.0 ?mol/h/gHb .
Intron 8 Splice Site c.820+13A>G p.D274Gfs*17 Pathogenic Rivera et al. (2014 submitted)
This variant was first reported by Kozak et al (1999). New study by Rivera el al (submitted in 2014) describes a Caucasian aldult male of Portuguese descent that was homozygous for c.820+13A>G. As a neonate, patient presented with jaundice, persisting vomiting, hepatomegaly and high levels of liver enzymes. At 1-month of age patient was diagnozed with galactosemia due to absent GALT enzyme activity. Minigene splicing assays in two distinct cell lines (HeLa and COS-7) and patient's transcript analyses showed that the c.820+13A>G mutation activates a cryptic donor splice site (c.820+14_820+15), inducing an aberrant splicing of the GALT pre-mRNA, which in turn leads to a frameshift with inclusion of a premature stop codon (p.D274Gfs*17). Functional-structural studies of the recombinant wild-type and truncated GALT showed that the latter is devoid of enzymatic activity and prone to aggregation (information was provided by personal communication with Dr. Rivera from the University of Lisbon). iarivera@ff.ul.pt
Intron 8 c.820+23T>G Benign Maceratesi (1996)
Intron 8 c.820+44G>C Uncertain Calderon et al, unpublished
Hispanic male with abnormal NBS was heterozygous for c.820+44G>C and the mutation c.253-2A>G. Patient presented with vomiting, failure to thrive, and enzyme activity of 4.3 µmol/h/Hgb.
Intron 8 c.820+58G>T Benign Kozak (1999)
Intron 8 c.821-23dupT Uncertain Calderon et al, unpublished
Female was heterozygous for the Duarte 2 mutations c.-119_116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, c.508-24G>A) and c.821-23dupT. Patient's enzyme activity was 7.2 µmol/h/Hgb.
Intron 8 Splice Site c.821-7A>G Exon 9 skip? Uncertain Choi et al 2014
Detected in a Korean female infant with c.286_299delGACAACGACTTCCC (one copy each). Enzyme activity was 7.3 ?mol/h/gHb. Patient was identified with abnormal NBS.
Intron 8 Splice Site c.821-2A>G Exon 9 skip Pathogenic Bosch (2005)
Exon 9 Deletion c.824del p.L275fs Pathogenic Elsas (1998)
Exon 9 Indel c.826_827delinsAA p.A276N Likely Pathogenic
Korean male infant was heterozygous for this variant and p.N314D. Enzyme activity was 5.9 ?mol/h/gHb. In silico analysis using Polyphen and SIFT indicate this variant is pathogenic.
Exon 9 Missense c.833T>A p.I278N Pathogenic Calderon (2007)
Two patients of unknown relation and erythrocyte GALT activities of 9.8 and 11.4 ?mol/h/gHb were heterozygous with this variant.
Exon 9 Missense c.836T>G p.M279R Pathogenic University of Bristol, unpublished
Exon 9 Missense c.836T>C p.M279T Uncertain
In our lab, two Caucasian males (twins) with abnormal NBS were heterozygous for p.M279T and the Duarte 2 mutations c.-119_116delGTCA, p.N314D (polymorphisms: c.378-27G>C, c.507+62G>A, --c.508-24G>A). One patient's enzyme activity was 8.2 µmol/h/Hgb and the other ranged from7-8µmol/h/Hgb.
Exon 9 Missense c.836T>C p.M279T Uncertain
see above: combined cases for twin boys
Exon 9 Missense c.844C>G p.L282V Pathogenic Tyfield (1999)
Exon 9 Missense c.854A>G p.K285R Pathogenic Ramandeep Singh et al, unpublished
Detected in an Indian patient presenting wiht persistent hypoglycemia, cholestasis, hepatosplenomegaly, thickened gall bladder, prolonged hyperbilirubinemia, decreased GALT activity and IU work up shows CMV infection. Submission contributed by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 9 Missense c.855G>T p.K285N Pathogenic Leslie (1992)
Also described in Papachristoforou et al. 2014. In our lab, a Caucasian female with abnormal NBS was heterozygous for p.K285N and the Duarte 2 haplotype. Enzyme activity was 6.9 µg/h/gHgb. Viggiano et al. 2015 described two patients of italian descent who were heterozygous for p.K285N and p.E271D or p.P244S respectively. Enzyme activity was less than 1 in both cases.
Exon 9 Missense c.858T>C p.Y286H Pathogenic Zaffanello (2005)
Exon 9 Silent c.864C>T p.N288N Uncertain Calderon et al, unpublished
African American female experiencing feeding problems was heterozygous for p.S135L, p.N288N (c.865C>T),and p.H315H (c.945T>C) and polymorphism p.T292T (c.876G>A). Enzyme activity was 1.8 µmol/h/Hgb.
Exon 9 Missense c.865C>T p.L289F Pathogenic Calderon (2007)
L289F heterozygous detected in a patient with erythrocyte GALT activity of 11.0 U/g Hgb
Exon 9 Missense c.866T>G p.L289R Pathogenic Tyfield (1999)
Exon 9 Missense c.871G>A p.E291K Pathogenic Tyfield (1999)
Exon 9 Missense c.872A>T p.E291V Pathogenic Calderon et al, unpublished
This mild mutation was detected in an 1 month old hispanic male together with Q188R (both heterozygous). Baby was first identified by an abnormal newborn screening. GALT enzyme activity was consistent with D/G galactosemia.
Exon 9 Silent c.876G>A p.T292T Benign Calderon et al, unpublished
Patient of Asian/Caucasian descent was heterozygous for p.T292T, p.H315H, and p.F171S (enzyme activity=1.7 ?mol/h/gHb). A second patient of African American descent and GALT enzyme activity of 3.8 ?mol/h/gHb was heterozygous for this silent variation, p.H315H, and p.S135L. In our laboratory we detected p.T292T in 3 out of 50 controls or 100 chromosomes and believe this is a common polymorphism.
Exon 9 Silent c.876G>A p.T292T Benign Calderon et al, unpublished
African-American female patient identified with abnormal NBS was heterozygous for p.F171S, S135L and the silent variants p.H315H and p.T292T. Enzyme activity was 1.7 ?mol/h/gHb.
Exon 9 Silent c.876G>A p.T292T Benign Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was 11.9 ?mol/h/gHb and GALT1-P was mildly elevated.
Exon 9 Silent c.876G>A p.T292T Benign Calderon et al, unpublished
African-American female patient identified with abnormal NBS was heterozygous for S135L and the silent variants p.H315H and p.T292T. Enzyme activity was 6.5 ?mol/h/gHb (tested in outside lab).
Exon 9 Silent c.876G>A p.T292T Benign Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was low (tested in outside lab) and GALT1-P was elevated.
Exon 9 Silent c.879C>T p.S293S Benign Calderon et al. unpublished
African-American male with abnormal NBS was heterozygous for this silent variant. No pathogenic GALT gene mutations were detected by sequencing. Another male with abnormal NBS was heterozygous for p.S293S and p.S135L. Enzyme activity was 10% of normal (tested in outside lab).
Exon 9 Missense c.881T>A p.F294Y Pathogenic Tyfield (1999)
Female with abnormal NBS was heterozygous for p.F294Y and the Duarte 2 mutations c.-119_116delGTCA, p.N314D. Patient presented with no clinical symptoms, had enzyme activity of 3.9 µmol/h/Hgb and elevated GAL-1-P.
Exon 9 Deletion c.882del p.F294fs Pathogenic Tyfield (1999)
Exon 9 Missense c.883C>A p.P295T Pathogenic University of Bristol, unpublished
Caucasian male with abnormal NBS was heterozygous for p.R231H and p.P295T. Enzyme activity was .
Exon 9 Missense c.896G>A p.G299D Uncertain Calderon et al, unpublished
Female identified with abnormal NBS was heterozygous for p.G299D. Patient presented with reduced enzyme activity but had no symptoms.
Intron 9 Splice Site c.904+3G>T Likely pathogenic Calderon et al, unpublished
African American female with abnormal NBS was heterozygous p.S135L and c.904+3G>T. Enzyme activity was 0.0 µmol/h/Hgb (outside lab) but patient presented no clinical symptoms.
Intron 9 Splice Site c.904+1G>T p.? Pathogenic Calderon el al, unpublished
Detected in a male child with the Duarte 2 variant (5-UTR-119_-116delGTCA; p.N314D; and intronic polymorphisms c.378-27G>C, c.507+62G>A, c.508-24G>A). Enzyme levels were concordant with D/G genotype.
Intron 9 Splice Site c.904+5G>A p.? Pathogenic Calderon et al, unpublished
African American female identified with abnormal newborn screening was heterozygous for this mutation (inherited from dad) and p.S135L (from mom). GALT enzyme activity was 0 umol/h/gHb.
Exon 10 Nonsense c.920C>A p.S307X Pathogenic Singh et al. (2011)
Newborn in India presenting with jaundice, poor feeding and lethargy, hepatosplenomegaly and distended abdomen with free fluid, bilateral cataracts, hydrocephalus, and acqueductal stenosis was observed was heterozygous for p.S307X (inherited from mother) and p.Q188R (inherited from dad). Patient's GALT enzyme activity was 17% of normal. Parents exhibited approximately 50% of normal enzyme activity. Patient improved after galactose free diet. Contact ramandeepsingh.83@gmail.com for more information.
Exon 10 Missense c.922G>A p.E308K Pathogenic Elsas (1998)
Exon 10 Missense c.940A>G p.N314D Benign
(Duarte1)
Mild (Duarte 2)
Reichardt (1991)
Referred to as the Duarte variant. When p.N314D occurs in cis with p.L218L it is referred to as Duarte 1 variant, usually causing an increase in enzyme activity. When this variant is present in cis with c.-119_-116del and intronic polymorphisms c.378-27G>C, c.507+62G>A, c.508-24G>A it is also referred to as the Duarte 2 variant. This haplotype is associated with a 25 percent reduction of GALT activity when heterozygous and 50 percent reduction when present in both alleles. See Kozak (1999) for more information.
Exon 10 Silent c.945T>C p.H315H Benign Lai (1996)
This silent variant was found in two patients in our lab with p.T292T: one was an Asian/Caucasian female with p.F171S and p.Q188R (no enzyme activity) ; the other was an African American patient with p.S135L (enzyme activity was 3.8 ?mol/h/gHb).
Exon 10 Silent c.945T>C p.H315H Benign Calderon et al, unpublished
African-American female patient identified with abnormal NBS was heterozygous for p.F171S, S135L and the silent variants p.H315H and p.T292T. Enzyme activity was 1.7 ?mol/h/gHb.
Exon 10 Silent c.945T>C p.H315H Benign Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was 11.9 micrograms and GALT-1-P was mildly elevated.
Exon 10 Silent c.945T>C p.H315H Benign Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was 11.9 ?mol/h/gHb and GALT1-P was mildly elevated.
Exon 10 Silent c.945T>C p.H315H Benign Calderon et al, unpublished
African-American male with abnormal newborn screening was heterozygous for p.S135L and the silent variantions p.T292T and p.H315H. Enzyme activity was low (tested in outside lab) and GALT1-P was elevated.
Exon 10 Nonsense c.947G>A? p.W316X? Pathogenic Sommer (1995)
Caucasian female patient with absent GALT enzyme activity was heterozygous for this mutation, p.Q188R, and the Duarte 2 haplotype.
Exon 10 Missense c.948G>A p.W316X Pathogenic Calderon et al, unpublished
Exon 10 Deletion c.949del p.Q317fs Pathogenic Tyfield (1999)
Exon 10 Missense c.950A>G p.Q317R Pathogenic Tyfield (1999)
Exon 10 Missense c.951G>T p.Q317H Pathogenic Tyfield (1999)
Exon 10 Deletion c.952del p.L318fs Pathogenic Elsas (1998)
Exon 10 Silent c.954G>A p.L318L Benign Maceratesi (1996)
Exon 10 Missense c.957C>A p.H319Q Pathogenic Reichardt (1993)
Exon 10 Silent c.957C>T p.H319H Uncertain Ramandeep Singh et al, unpublished
Submission by Ramandeep Singh, Gurjit Kaur, Babu Ram Thapa, Rajendra Prasad. Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Contact ramandeepsingh.83@gmail.com.
Exon 10 Missense c.958G>A p.A320T Pathogenic Elsas (1995)
Exon 10 Missense c.959C>T p.A320V Suspected Pathogenic Calderon et al. unpublished
Caucasian male with abnormal NBS, high GAL-1-P, abnormal liver function and coagulation factors, and absent GALT enzyme activity, was heterozygous for both this mutation and p.K285N.
Exon 10 Missense c.961C>T p.H321Y Pathogenic Webb (2003)
Detected in a patient with p.S293F. p.H321Y was described in the literature as a leaky mutation due to absent GALT enzyme activity in erythrocytes but residual in vivo enzyme activity, abolishing total body galactose oxidation to a lesser degree. Publication describes mutation at the protein level only.
Exon 10 Missense c.961C>T p.H321Y Pathogenic Calderon et al. unpublished
Asian female identified with abnormal NBS, presenting with hyperbilirubinemia, was homozygous for p.H321Y. Enzyme activity was . Family history revealled a maternal aunt with three unexplained infant deaths.
Exon 10 Missense c.967T>C p.Y323H Pathogenic Tyfield (1999)
Exon 10 Missense c.967T>G p.Y323D Pathogenic Elsas (1995)
Exon 10 Missense c.968A>G p.Y323C Pathogenic Dobrowski (2005)
Dobrowski et al identified a patient heterozygous for p.Y323C, the LA variant (p.[N314D;L218L]), and GALT enzyme activity consistent with a D/G phenotype. A second male patient, of mixed Caucasian ethnicity, was identified via newborn screening but not showing any clinical symtpoms of galactosemia; GALT enzyme activity of 4.1 umol/h/gHb and heterozygous for p.Y323C (c.968A>G) and the LA variant. Male patient diagnozed with galactosemia and observing a galactose-free diet was experiencing vomitting. Enzyme activity was . Patient was found to be homozygous for p.Y323C and the Duarte 2 haplotype.
Exon 10 Missense c.970C>T p.P324S Pathogenic Boleda (1995)
Exon 10 Silent c.972T>C p.P324P Benign Maceratesi (1996)
Exon 10 Missense c.974C>T? p.P325L? Pathogenic Greber-Platzer (1997)
Male patient was heterozygous for this mutation and the Duarte 2 haplotype.
Exon 10 Deletion c.976del p.L326fs Pathogenic University of Bristol, unpublished
Exon 10 Deletion c.979del p.L327fs Pathogenic Elsas (1998)
Exon 10 Missense c.980T>C p.L327P Pathogenic Calderon et al, unpublished
This mutation was detected in the heterozygous form in a sample with no detectable erythrocyte GALT activity. This patient was also heterozygous for Q188R.
Exon 10 Missense c.982C>T p.R328C Suspected Pathogenic Calderon et al, unpublished
Female presenting with very low enzyme activity was heterozygous for p.R328C and p.K285C.
Exon 10 Missense c.983G>A p.R328H Pathogenic Elsas (1998)
Exon 10 Missense c.986C>T p.S329F Pathogenic Tyfield (1999)
Exon 10 Missense c.989C>T p.A330V Pathogenic Sommer (1995)
Exon 10 Missense c.997C>G p.R333G Pathogenic Leslie (1992)
Caucasian female identified with abnormal NBS was heterozygous for p.Y209C and p.R333G (tested in our lab). Enzyme activity was reported to be low (tested in outside laboratory).
Exon 10 Missense c.997C>T p.R333W Pathogenic Reichardt (1991)
Structural and function impact of this mutation can be found in Proc Natl Acad Sci. 93(14):7166-71; Christacos & Fridovich-Keil 2002. Mol Genet Metab.76(4):319-26. Also, a patient was heterozygous for this mutation and homozygous for the Duarte 2 haplotype.
Exon 10 Missense c.997C>T p.R333W Pathogenic Calderon et al, unpublished
Female with abnormal NBS was heterozygous for p.R333W and p.M142K. Enzyme activity was .
Exon 10 Missense c.997C>T p.R333W Pathogenic Calderon et al, unpublished
Caucasian-Russian female identified with abnormal NBS was heterozygous for p.R333W and the Duarte 2 haplotype. Enzyme activity was 3.5 ?mol/h/gHb and GAL-1-P was within the normal range.
Exon 10 Missense c.997C>T p.R333W Pathogenic Viggiano et al. 2015
Italian child (3 yr-old) was heterozygous for p.R333Q and the Duarte 2 haplotype. Patient had no symptoms of galactosemia at diagnosis (newborn) and outcome at present was normal. Enzyme activity was consistent with D/G.
Exon 10 Missense c.998G>A p.R333Q Pathogenic Hirokawa (1999)
Exon 10 Missense c.998G>A p.R333Q Pathogenic Choi et al 2014
Korean female infant was heterozygous for p.R333Q and p.Y165H. Enzyme activity was 6.3 ?mol/h/gHb.
Exon 10 Missense c.998G>A p.R333Q Pathogenic Choi et al 2014
Korean male infant was homozygous for this mutation. Enzyme activity was 1.8 ?mol/h/gHb.
Exon 10 Missense c.998G>T p.R333L Pathogenic Singh et al, unpublished
This variation was detected in an Indian patient presenting with persistent jaundice and vomiting, intrahepatic cholestasis, fibrosis, poor feeding, lethargy and bilateral catarats. Submitted by R. Singh et al. from the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, Chandigah, India. Contact ramandeepsingh.83@gmail.com for more information.
Exon 10 Missense c.1001A>G p.K334R Pathogenic Leslie (1992)
Exon 10 Missense c.1006A>T p.M336L Pathogenic Elsas (1998)
Male with abnormal NBS and high GAL-1-P was heterozygous for this mutation and the splice variant c.253-2A>G.
Exon 10 Silent c.1014C>G p.G338G Uncertain Tyfield (1999)
Detected in a female patient with p.Q188R and no other mutations by sequencing. This patient presented with developmental delay and enzyme activity of 0.9 umol/h/gHb.
Exon 10 Silent c.1014C>G p.G338G Uncertain Calderon et al, unpublished
Hispanic male with known family history of galactosemia and abnormal NBS was heterozygous for p.G338G and Duarte 2 haplotype. Enzyme activity was 7.5 ?mol/h/gHb.
Exon 10 Missense c.1018G>A p.E340K Pathogenic University of Bristol, unpublished
Exon 10 Nonsense c.1018G>T p.E340X Pathogenic Gathof (1995)
Exon 10 Missense c.1024C>A p.L342I Pathogenic Item (2002)
Exon 10 Missense c.1030C>A p.Q344K Pathogenic Elsas (1998)
Caucasian female with abnormal NBS was heterozygous for p.L37P and p.Q344K. Clinical findings included vomiting and jaundice. Enzyme activity was 0.0 µmol/h/Hgb.
Exon 10 Missense c.1034C>A p.A345D Pathogenic University of Bristol, unpublished
Asian-Vietnamese female identified with abnormal NBS was heterozygous for p.A345D. Enzyme activity was 12.9 ?mol/h/gHb.
Exon 10 Deletion c.1047del p.L349fs Pathogenic University of Bristol, unpublished
Exon 10 Missense c.1048A>G p.T350A Pathogenic Shin (1996)
Exon 10 Deletion c.1051del p.P351fs Pathogenic University of Bristol, unpublished
Exon 10 Nonsense c.1057C>T p.Q353X Pathogenic University of Bristol, unpublished
Intron 1 Splice Site c.82+3A>G Pathogenic De Lucca, M et.al. 2017
Ecuadorian patient presented an abnormal level of total galactose in blood of 13.03 mg/dl (the reference for 0 to 1 month is <7.2mg/dl), thus confirming a galactosemia diagnosis. The c.82+3A>G was in homozygosis. The c.82+3A>G variation is located next to the canonical donor signal of intron 1, therefore, to look for a possible effect on the splicing process the integrated software ALAMUT V.2.0 was used. The five algorithms used to evaluate the effect of the c.82+3A>G mutation showed a reduction of the score of the natural donor splice site (7.53 for the wild-type sequence vs 5.33 for the new sequence), probably inducing the use of an alternative donor site in intron 1. A modification of ESE patterns was also predicted by increasing the score for the Srp40 element. Therefore, the c.82+3A>G alteration may be considered as a pathogenic variant.
Intron 10 c.1059+24G>A Uncertain Calderon et al, unpublished
Possible polymorphism.
Intron 10 c.1059+36T>A Benign Tyfield (1999)
Intron 10 Splice Site c.1059+56C>T p.Q353_A354ins
VRTQNSLASPDSHMQYVQ
Pathogenic Wadelius (1993)
Cryptic donor splice site activation: causing insertion of 54 intronic bases at the end of exon 10 coding for amino acids (NCBI ref seq S65770)
Intron 10 Splice Site c.1060-1G>A Pathogenic Calderon et al, unpublished
Detected in a male patient with the Duarte 2 haplotype and enzyme activity of 4.8 umol/h/gHb. This mutation is expected to affect normal splicing of exon 11.
Exon 11 Deletion c.1070_1071delGA p.R357TfsX6 Pathogenic Calderon et al, unpublished
Male with abnormal NBS and presenting no clinical symptoms was heterozygous for p.M129L and homozygous for c.1070_1071delGA (p.R357TfsX6). Enzyme activity was 3.5 µmol/h/Hgb.
Exon 11 Nonsense c.1072delC? p.L358X Pathogenic Webb (2003)
Detected in a patient with p.Q188R. Described to impair GALT enzyme activity and total body galactose oxidation significantly. Publication describes mutation at the protein level only.
Exon 11 Indel c.1078_1083
delins20
Pathogenic Calderon et al, unpublished
Caucasian female patient presenting no clinical symptoms of galactosemia was heterozygous for this frameshift mutation and the Duarte 2 haplotype (Enzyme activity=8.7 umol/h/gHb).
Exon 11 Missense c.1087G>A p.E363K Uncertain Calderon et al. unpublished
Asian/Oriental male with abnormal NBS and GALT enzyme activity of 2.8 ?mol/h/gHb was heterozygous for both this variant and p.R258C.
Exon 11 Missense c.1087G>A p.E363K Likely Pathogenic Choi et al 2014
Korean female infant was heterozygous for this variation. Enzyme activity was 16.4 ?mol/h/gHb.
Exon 11 Nonsense c.1098C>A p.Y366X Pathogenic Greber-Platzer (1997)
Exon 11 Missense c.1103T>C p.L368P Mildly Pathogenic Calderon et al, unpublished
Caucasian male identified with abnormal NBS was heterozygous for p.L368P and p.Q188R. Enzyme activity was low (6.7 ?mol/h/gHb) and GAL-1-P was high.
Exon 11 Nonsense c.1108C>T p.Q370X Pathogenic University of Bristol, unpublished
Exon 11 Missense c.1132A>G p.I378V Pathogenic University of Bristol, unpublished
Caucasian female with abnormal NBS was heterozygous for p.E271G and p.Q188R and p.I378V. Patient had no known family history of galactosemia and presented with jaundice, abnormal coagulations, and high Gal-1P. Enzyme activity was 0 µmol/h/gHgb.
Exon 11 no-stop change? c.1138T>C p.X380RextX50 Pathogenic Tyfield (1999)
See also Kozak et al 1999. Hum Mut 15(2):206
Exon 11 no-stop change? c.1140A>C p.X380Cext50 Pathogenic Bosch (2005)
3'UTR c.1140+203C>T Benign Calderon et al, unpublished
This variant, suspected to be benign, was detected in a male patient heterozygous for p.D98N and p.Q188R. Caucasian female was heterozygous for this variant (possibly a polymorphism?). Another female patient with no symptoms was heterozygous for this variation and p.Q188R.
3'UTR c.*8G>A Uncertain Calderon et al, unpublished
Female with abnormal NBS and no clinical symptoms was homozygous for c.*8G>A. Enzyme activity was 10.1 µmol/h/Hgb.
3'UTR c.*111A>G No Effect? Calderon et al, unpublished
Female with abnormal NBS was heterozygous for c.*111A>G. Patient received a blood transfusion 3 days after birth and presented no clinical symptoms. Enzyme activity was reported to be low (outside lab)
3'UTR c.*147A>G Benign Calderon et al, unpublished
Female with abnormal NBS was heterozygous for c.1140+147A>G. Patient was on lactose-free diet and had no family history of galactosemia. GAL-1P was 0.3mg/dL and enzyme activity was 26.4 µmol/h/gHgb. Outside lab reported low to normal enzyme activity.