GM20074

GM20074 LCL from B-Lymphocyte

Description:

LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM (OVARIOLEUKODYSTROPHY, INCLUDED)
EUKARYOTIC TRANSLATION INITIATION FACTOR 2B, SUBUNIT 2; EIF2B2

Affected:

Yes

Sex:

Male

Age:

21 YR (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

Family Member

Relation to Proband

brother

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; head circumference at birth 33.5 cm; walked at 12 months; spoke first words at 12-13 months; instability and imbalance began at 12 months; developed slowly progessive spastic paraparesis with marked impairment in coordination, balance and ambulation; in wheelchair by age 5; impaired speech with a slowed, spastic quality; regression in functional status after flu or fever; needs magnification for vision; isolated episode of dysphagia; diffuse cavitation of white matter on MRI; donor subject is a compound heterozygote: one allele has an A>G transition at nucleotide 638 of the EIF2B2 gene [638A>G] resulting in a substitution of glycine for glutamic acid at codon 213 [Glu213Gly(E213G)] and a second allele has a G>C transversion at nucleotide 910 of the EIF2B2 gene [910G>C] resulting in a substitution of a termination codon for glutamic acid at codon 304[Glu304Ter(E304X)]; affected sibling is GM20073.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

EIF2B2

Chromosomal Location

14q24

Allelic Variant 1

606454.0001; LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER

Identified Mutation

GLU213GLY; In 2 distantly related individuals with VWM (603896), Leegwater et al. (2001) found homozygosity for an glu213-to-gly (E213G) mutation in the EIF2B2 gene. Heterozygosity for the same mutation was found in a patient in the United State who shared a part of the haplotype on 14q24 with the homozygous patients observed in Europe, suggesting a familial relationship. The second mutation predicted a V316D amino acid substitution (606454.0002). The Dutch patients with VWM due to the mutation in EIF2B2 came from the southern part of the Netherlands rather than the eastern part, where the patients with the T91A mutation in the EIF2B5 gene (603945.0001) lived.

Gene

EIF2B2

Chromosomal Location

14q24

Allelic Variant 2

E304X; LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER

Identified Mutation

GLU304TER

Phenotypic Data

Remarks

Publications

Moon SL1, Parker R2,3., Analysis of eIF2B bodies and their relationships with stress granules and P-bodies Scientific Reports:8 2018

PubMed ID: 30115954

Fogli A, Schiffmann R, Bertini E, Ughetto S, Combes P, Eymard-Pierre E, Kaneski CR, Pineda M, Troncoso M, Uziel G, Surtees R, Pugin D, Chaunu MP, Rodriguez D, Boespflug-Tanguy O, The effect of genotype on the natural history of eIF2B-related leukodystrophies. Neurology62(9):1509-17 2004

PubMed ID: 15136673