GM16824

GM16824 LCL from B-Lymphocyte

Description:

ALEXANDER DISEASE
GLIAL FIBRILLARY ACIDIC PROTEIN; GFAP

Affected:

Yes

Sex:

Male

Age:

23 MO (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of the Nervous System

Biopsy Source

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Line ALX-1; floppy at birth; macrocephalic; at one month abnormal eye movements (sun-downing); CAT scan at two months showed borderline hydrocephalus and at four months decreased density white matter; by 11 months MRI showed frontal leukodystrophy; onset of seizures at 13 months; nasogastric tube at 16 months; respiratory, then cardiac arrest and death at 30 months; autopsy confirmed diagnosis; donor subject is heterozygous for a mutation in codon 239 of the GFAP gene; a C-to-T transition at nucleotide 729 (729C>T) results in an arg239-to-cys mutation [ARG239CYS (R239C)].

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

GFAP

Chromosomal Location

17q21

Allelic Variant 1

137780.0001; ALEXANDER DISEASE

Identified Mutation

ARG239CYS; Brenner et al. [Nature Genet. 27: 117-120 (2001)] found that 5 unrelated patients with Alexander disease (203450) were heterozygous for mutations in codon 239 of the GFAP gene. In 4 of these, a C-to-T transition at nucleotide 729 led to an arg239-to-cys mutation (R239C). Age at death in these 4 patients varied from 4 years to 11 years.