GM19988

GM19988 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Female

Age:

36 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

Relation to Proband

proband

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically affected; patient #944 in Fogli et al, Am J Hum Genet 72:1544-1550, 2003; bilateral cataracts in first week of life were excised with implantation of intraocular lens; walked at age 12 mo; difficulties in school; mild developmental delay; mild thoracic dextroscoliosis; bilateral pes cavus; menarche at age 14 yr; amenorrhea at age 26 yr; atrophied ovaries; spasticity; gait instability at age 25 yr; walker used at age 30 yr; hypophonia with mild dysarthria observed; tongue weakness and hyperreflexia; sphincter disfunction at age 26 yr; optic atrophy; visual loss at age 28 yr;glaucoma with arcuate scotoma of left eye; IQ=65 at age 30 yr; MRI showed generalized volume loss of cortex and white matter; microcephaly; visual motor difficulties; poor executive function; donor subject is a compound heterozygote: one allele has a C>T transition at nucleotide 512 of the EIF2B2 gene (512C>T), resulting in a ser171-to-phe mutation [Ser171Phe (S171F)] and the second allele has a 6 bp deletion (ATGGCT)/2 bp insertion (TG) at nucleotide 607, resulting in a frameshift at met203

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

EIF2B2

Chromosomal Location

14q24

Allelic Variant 1

606454.0004; OVARIOLEUKODYSTROPHY

Identified Mutation

SER171PHE; In a patient with ovarioleukodystrophy (603896), Fogli et al. (2003) identified a C-to-T transition at nucleotide 512 of the EIF2B2 gene, resulting in a ser171-to-phe mutation (S171F), in compound heterozygous state with a 6-bp deletion (ATGGCT)/2-bp insertion (TG) at nucleotide 607, resulting in a frameshift at met203 (606454.0005). Secondary amenorrhea began at age 26 years in the patient.

Gene

EIF2B2

Chromosomal Location

14q24

Allelic Variant 2

606454.0005; OVARIOLEUKODYSTROPHY

Identified Mutation

6-BP DEL/2-BP INS, NT607; See 606454.0004 and Fogli et al. (2003).

Phenotypic Data

Remarks

Publications

Fogli A, Rodriguez D, Eymard-Pierre E, Bouhour F, Labauge P, Meaney BF, Zeesman S, Kaneski CR, Schiffmann R, Boespflug-Tanguy O, Ovarian failure related to eukaryotic initiation factor 2B mutations. Am J Hum Genet72(6):1544-50 2003

PubMed ID: 12707859