GM11763

GM11763 LCL from B-Lymphocyte

Description:

GALACTOSEMIA
GALACTOSE-1-PHOSPHATE URIDYLYLTRANSFERASE; GALT

Affected:

Yes

Sex:

Male

Age:

30 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Carbohydrate Metabolism

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Family Member

Relation to Proband

proband

Confirmation

Molecular characterization after cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Despite well documented adequate dietary management since birth, suffers from severe neurologic complications; sim affec bro; mRNA & CRM pos; GALT gene mutations: A to G transition at nucleotide 591 (591A>G) [Gln188Arg (Q188R)] & C to T transition at nucleotide 1025 (1025C>T) [Arg333Trp (R333W)]

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

GALT

Chromosomal Location

9p13

Allelic Variant 1

606999.0006; GALACTOSEMIA

Identified Mutation

GLN188ARG; Reichardt et al. [Am J Hum Genet 49: 860 (1991)] demonstrated a transition at nucleotide 591 that substituted arginine for glutamine-188. The mutated glutamine is not only highly conserved in evolution, but is also 2 amino acid residues downstream from the active site histidine-proline-histidine triad. Lymphoblasts from subjects homozygous for the GLN188ARG mutation show essentially no detectable GALT activity [Fridovich-Keil and Jinks-Robertson. Proc Nat Acad Sci USA 90: 398 (1993)].

Gene

GALT

Chromosomal Location

9p13

Allelic Variant 2

606999.0002; GALACTOSEMIA

Identified Mutation

ARG333TRP; In a classic galactosemic patient, Reichardt and Woo [Am J Hum Genet 47: A164 (1990); Proc Natl Acad Sci U S A 88: 2633 (1991)] found a methionine-to-lysine change at a position that is conserved in all eukaryotes sequenced to date but in none of the prokaryotes. The mutation reduced the specific activity of the mutated protein to about 4% of normal.

Phenotypic Data

Remarks

Publications

Reichardt JK, Packman S, Woo SL, Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase. Am J Hum Genet49:860-7 1991

PubMed ID: 1897530

Lo W, Packman S, Nash S, Schmidt K, Ireland S, Diamond I, Ng W, Donnell G, Curious neurologic sequelae in galactosemia. Pediatrics73:309-12 1984

PubMed ID: 6701054