GM21645

GM21645 Fibroblast from Skin, Unspecified

Description:

CEREBROOCULOFACIOSKELETAL SYNDROME 4; COFS4
EXCISION-REPAIR, COMPLEMENTING DEFECTIVE, IN CHINESE HANSTER, 1; ERCC1

Affected:

No

Sex:

Male

Age:

No Data

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

White

Ethnicity

ITALIAN

Family Member

Relation to Proband

father

Confirmation

Molecular characterization before cell line submission to CCR

Species

Homo sapiens

Common Name

Human

Remarks

Clinically normal father of an affected son; donor subject is heterozygous for a C>G transversion at nucleotide 839 in exon 7 of the ERCC1 gene (839C>G) resulting in the subsitution of leucine for phenylalanine at codon 231 [Phe231Leu (F231L)]; proband is not in Repository

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin confirmed by LINE assay

Gene

ERCC1

Chromosomal Location

19q13.2-q13.3

Allelic Variant 1

126380.0002; CEREBROOCULOFACIOSKELETAL SYNDROME 4

Identified Mutation

PHE231LEU; In an infant with a severe and developmental disorder compatible with the diagnosis of cerebrooculofacioskeletal syndrome (COFS4; 610758), Jaspers et al. (Am J Hum Genet 80:457-466,2007) found compound heterozygosity for 2 mutations in the ERCC1 gene: a C-to-T transition predicted to convert codon gln158 into an amber translational stop signal (CAG to TAG; Q158X), inherited from the mother; inherited from the father, a C-to-G transversion which was predicted to change phe231 to leucine (F231L). The allele derived from the mother encoded a truncated polypeptide that lacked the entire C-terminal domain, which is essential for interaction with XPF. Heterodimerization of ERCC1-XPF is required for stability of the complex and for its endonuclease activity. Therefore, the Q158X allele was expected to be functionally null.