NA00433
DNA from Fibroblast
Description:
GALACTOSEMIA
GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE; GALT
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Carbohydrate Metabolism |
| Quantity |
50 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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Black/African American
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| Passage Frozen |
3 |
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| Gene |
GALT |
| Chromosomal Location |
9p13 |
| Allelic Variant 1 |
606999.0010; GALACTOSEMIA |
| Identified Mutation |
SER135LEU; Baker et al. (1966) described black patients with classic galactosemia who lacked GALT activity in their erythrocytes and yet were able to oxidize a substantial amount of labeled galactose to CO2 in vivo (Segal and Cuatrecasas, 1968). Liver and intestinal mucosa biopsy specimens from these patients expressed about 10% of normal GALT activity. This apparent tissue specificity of GALT enzyme expression was labeled the 'negro variant' of galactosemia. Lai et al. (1996) demonstrated that the underlying mutation is a C-to-T transition at bp1158 of the GALT gene that results in a serine-to-leucine substitution at codon 135 (S135L). Population screening was performed using a restriction enzyme assay; the mutation abolishes a TAQI recognition site. The S135L mutation was not found in 84 white patients with homozygous galactosemia or in 87 white control subjects without galactosemia. One S135L allele was found out of the 100 GALT alleles in 50 black subjects; 16 out of 32 alleles in 16 galactosemic patients were of the S135L type. (Also in 1 patient with galactosemia, the S135L mutation was maternal in origin; the patient had a black mother and a white father.)
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| Gene |
GALT |
| Chromosomal Location |
9p13 |
| Allelic Variant 2 |
606999.0010; GALACTOSEMIA |
| Identified Mutation |
SER135LEU; Baker et al. (1966) described black patients with classic galactosemia who lacked GALT activity in their erythrocytes and yet were able to oxidize a substantial amount of labeled galactose to CO2 in vivo (Segal and Cuatrecasas, 1968). Liver and intestinal mucosa biopsy specimens from these patients expressed about 10% of normal GALT activity. This apparent tissue specificity of GALT enzyme expression was labeled the 'negro variant' of galactosemia. Lai et al. (1996) demonstrated that the underlying mutation is a C-to-T transition at bp1158 of the GALT gene that results in a serine-to-leucine substitution at codon 135 (S135L). Population screening was performed using a restriction enzyme assay; the mutation abolishes a TAQI recognition site. The S135L mutation was not found in 84 white patients with homozygous galactosemia or in 87 white control subjects without galactosemia. One S135L allele was found out of the 100 GALT alleles in 50 black subjects; 16 out of 32 alleles in 16 galactosemic patients were of the S135L type. (Also in 1 patient with galactosemia, the S135L mutation was maternal in origin; the patient had a black mother and a white father.)
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| Remarks |
Fibroblasts accumulate large amounts of intracellular gal-1-phosphate and galactitol; donor subject is homozygous for a C>T transition at nucleotide 404 in exon 5 of the GALT gene (c.404C>T) resulting in a substitution of leucine for serine at codon 135 [Ser135Leu (S135L)] |
| Brophy ML, Stansfield JC, Ahn Y, Cheng SH, Murphy JE, Bell RD, AAV-mediated expression of galactose-1-phosphate uridyltransferase corrects defects of galactose metabolism in classic galactosemia patient fibroblasts Journal of inherited metabolic disease: 2021 |
| PubMed ID: 34918784 |
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| Reichardt JK, Molecular analysis of 11 galactosemia patients. Nucleic Acids Res19:7049-52 1991 |
| PubMed ID: 1766867 |
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| Schaub J, Shin-Buehring Y, Wiese B, Rahm P, Haas B, Metabolism of galactose and accumulation of galactose-1-phosphate in various cell types of cultured fibroblasts for galactosemia. pp. 319- 27. Models for the study of inborn errors of metabolism19:7049-52 1979 |
| PubMed ID: 376643 |
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