GM01629

GM01629 Fibroblast from Skin, Buttock

Description:

COCKAYNE SYNDROME, TYPE B; CSB
EXCISION-REPAIR CROSS-COMPLEMENTING, GROUP 6; ERCC6

Affected:

Yes

Sex:

Female

Age:

10 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Class

Repair Defective and Chromosomal Instability Syndromes

Biopsy Source

Buttock

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Buttock

Race

White

Country of Origin

USA

Family Member

Family History

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Culture is a poor grower; subject is clinically affected with complementation group B; upon examination at 2 years of age, the subject weighed 20 lbs and displayed the following symptoms: mild retardation, decreased muscle mass, poor coordination, spastic diplegia, dermal photosensitivity, nystagmus, hyperpigmented retina, skull size was noted to be at the lower limits of normal, posterior wedging of the T6 - T10 vertebral bodies, steep iliac angle, slight sclerosis of the ossification center of the greater trochanters, slight angulation of the radial head, enlarged elbow joint and contracture; by age 4 years old, symptoms progressed into the fully developed syndrome and additional symptoms included: lack of skull growth, splenomegaly, and slight enlargement of kidney (See Case IV in publication by Riggs, et al - PMID: 4641186); fibroblasts have decreased post UV light and X-ray colony-forming ability (see line CS1BE referenced in several publications); donor subject is a compound heterozygote: one allele has a C>T transition at nucleotide 2087 in exon 10 of the ERCC6 gene (2087C>T) resulting in the substitution of tryptophan for arginine at codon 670 [Arg670Trp (R670W)]; a second allele has a 1 bp deletion at nucleotide 3615 in exon 18 (3615delA) causing a frameshift beginning at codon 1179 and ending with a stop codon at 1200 (1179fsX1200) (refer to CS1BE in publication by Mallery, etc al – PMID: 9443879); subject’s unaffected father is GM02474 (Lymph).

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

Gene

ERCC6

Chromosomal Location

10q11

Allelic Variant 1

R670W; COCKAYNE SYNDROME, TYPE B

Identified Mutation

ARG670TRP

Gene

ERCC6

Chromosomal Location

10q11

Allelic Variant 2

1179fsX1200; COCKAYNE SYNDROME, TYPE B

Identified Mutation

3615delA

Phenotypic Data

Remarks

Publications

Rajkumar-Calkins AS, Szalat R, Dreze M, Khan I, Frazier Z, Reznichenkov E, Schnorenberg MR, Tsai YF, Nguyen H, Kochupurakkal B, D'Andrea AD, Shapiro GI, Lazaro JB, Mouw KW, Functional profiling of nucleotide Excision repair in breast cancer DNA repair82:102697 2019

PubMed ID: 31499327

Tuo J, Jaruga P, Rodriguez H, Bohr VA, Dizdaroglu M, Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8-hydroxyguanine and 8-hydroxyadenine resulting from oxidative stress. FASEB J17(6):668-74 2003

PubMed ID: 12665480

Cleaver JE, Thompson LH, Richardson AS, States JC, A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat14(1):9-22 1999

PubMed ID: 10447254

Mallery DL, Tanganelli B, Colella S, Steingrimsdottir H, van Gool AJ, Troelstra C, Stefanini M, Lehmann AR, Molecular analysis of mutations in the CSB (ERCC6) gene in patients with Cockayne syndrome. Am J Hum Genet62(1):77-85 1998

PubMed ID: 9443879

Jaeken J, Klocker H, Schwaiger H, Bellmann R, Hirsch-Kauffmann M, Schweiger M, Clinical and biochemical studies in three patients with severe early infantile Cockayne syndrome. Hum Genet83:339-46 1989

PubMed ID: 2478446

Lehmann AR, Three complementation groups in Cockayne syndrome. Mutat Res106:347-56 1982

PubMed ID: 6185841

Rainbow AJ, Howes M, A deficiency in the repair of UV and gamma-ray damaged DNA in fibroblasts from Cockayne's syndrome. Mutat Res93:235-47 1982

PubMed ID: 7062933

Chan GL, Little JB, Cross-sensitivity of certain xeroderma pigmentosum and Cockayne syndrome fibroblast strains to both ionizing radiation and ultraviolet light. Mol Gen Genet181:562-3 1981

PubMed ID: 6943407

Tanaka K, Kawai K, Kumahara Y, Ikenaga M, Okada Y, Genetic complementation groups in cockayne syndrome. Somatic Cell Genet7:445-55 1981

PubMed ID: 7280930

Andrews AD, Barrett SF, Yoder FW, Robbins JH, Cockayne's syndrome fibroblasts have increased sensitivity to ultraviolet light but normal rates of unscheduled DNA synthesis. J Invest Dermatol70:237-9 1978

PubMed ID: 641373

Riggs W Jr, Seibert J, Cockayne's syndrome. Roentgen findings. Am J Roentgenol Radium Ther Nucl Med116:623-33 1972

PubMed ID: 4641186