GM16825

GM16825 Fibroblast from Skin, Unspecified

Description:

ALEXANDER DISEASE
GLIAL FIBRILLARY ACIDIC PROTEIN; GFAP

Affected:

Yes

Sex:

Male

Age:

6 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of the Nervous System

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Line ALX-2; slightly floppy with poor eye contact in the first year; at 18 months increasing head size and beginning of regression. MRI at 2.5 years showed white matter deterioration and ventricular cyst; first seizure at age 3.5 years; at 5.5 years had frequent and longer seizures and swallowing difficulties; died at 6 years, 3 months of age; autopsy confirmed the 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.

Phenotypic Data

Remarks

Publications

Li L1, Tian E2, Chen X2, Chao J2, Klein J2, Qu Q2, Sun G3, Sun G2, Huang Y2, Warden CD4, Ye P2, Feng L2, Li X2, Cui Q2, Sultan A2, Douvaras P5, Fossati V5, Sanjana NE6, Riggs AD3, Shi Y7., GFAP Mutations in Astrocytes Impair Oligodendrocyte Progenitor Proliferation and Myelination in an hiPSC Model of Alexander Disease Cell Stem Cell23:239-251 2018

PubMed ID: 30075130

Kondo T, Funayama M, Miyake M, Tsukita K, Era T, Osaka H, Ayaki T, Takahashi R, Inoue H, Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes Acta neuropathologica communications4:69 2016

PubMed ID: 27402089

Brenner M, Johnson AB, Boespflug-Tanguy O, Rodriguez D, Goldman JE, Messing A, Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nat Genet27(1):117-20 2001

PubMed ID: 11138011

Messing A, Goldman JE, Johnson AB, Brenner M, Alexander disease: new insights from genetics. J Neuropathol Exp Neurol60(6):563-73 2001

PubMed ID: 11398833