GM13370

GM13370 Fibroblast

Description:

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP G; XPG
EXCISION-REPAIR, COMPLEMENTING DEFECTIVE, IN CHINESE HAMSTER, 5; ERCC5

Affected:

Yes

Sex:

Male

Age:

2 YR (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Nucleotide and Nucleic Acid Metabolism

Class

Repair Defective and Chromosomal Instability Syndromes

Cell Type

Fibroblast

Transformant

Untransformed

Race

White

Ethnicity

FLEMISH

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

XPCS2LV; clinical characteristics of Cockayne syndrome with biochemical defect typical of XP; severe psychomotor retardation and microcephaly; dysplastic ears; large extremities; absent visual and auditory-evoked potentials; salt-and-pepper retinal pigmentation; donor subject is a compound heterozygote: one allele has a 1 bp deletion in an AAA triplet at nucleotides 2170_2172 of the ERCC5 gene resulting in a TGA stop codon after amino acid 659 (fs660Ter)and a second allele has a C>T transition at nucleotide 984 (984C>T) resulting in the substitution of a termination signal for arginine at codon 263 [Arg263Ter (R263X)]

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis

Gene

ERCC5

Chromosomal Location

13q33

Allelic Variant 1

133530.0004; XERODERMA PIGMENTOSUM, GROUP G COMBINED WITH COCKAYNE SYNDROME

Identified Mutation

1-BP DEL, FS660TER; Nouspikel et al. (1997) studied a girl with psychomotor retardation and microcephaly who died at 6.5 years of age. She was severely sunlight-sensitive with several pigmented cutaneous spots (Jaeken et al., 1989; Vermeulen et al., 1993). She was lacking a single nucleotide within an AAA triplet at nucleotides 2170-2172, which resulted in a TGA stop codon after amino acid 659. Such a deletion was considered characteristic of a slippage error during DNA replication. The patient appeared to be homozygous for this truncation mutation.

Gene

ERCC5

Chromosomal Location

13q33

Allelic Variant 2

133530.0005; XERODERMA PIGMENTOSUM, GROUP G COMBINED WITH COCKAYNE SYNDROME

Identified Mutation

ARG263TER; Nouspikel et al. (1997) studied fibroblasts from a male with extreme microcephaly, dysmorphism, and sun-sensitive skin with several pigmented spots who died at the age of 20 months. To their surprise they found that one XPG allele carried the same single nucleotide deletion as that found in homozygous state in the girl described in 113530.0004. Although both Flemish, these 2 patients were not known to be related; however, they possessed a very rare HLA haplotype in common. The second XPG allele in the male contained a C-to-T transition at nucleotide 984, converting arg263 into a TGA stop codon and resulting in an even more severely truncated protein. This transition was located within a CpG dinucleotide and thus may have resulted from deamination of a 5-methylcytosine. Thus the male patient was a compound heterozygote.

Phenotypic Data

Remarks

Publications

Arab HH, Wani G, Ray A, Shah ZI, Zhu Q, Wani AA, Dissociation of CAK from core TFIIH reveals a functional link between XP-G/CS and the TFIIH disassembly state PloS one5:e11007 2010

PubMed ID: 20543986

Fishel ML, Gamcsik MP, Delaney SM, Zuhowski EG, Maher VM, Karrison T, Moschel RC, Egorin MJ, Dolan ME, Role of glutathione and nucleotide excision repair in modulation of cisplatin activity with O6-benzylguanine Cancer chemotherapy and pharmacology55:333-42 2004

PubMed ID: 15723259

Dianov GL, Thybo T, Dianova II, Lipinski LJ, Bohr VA, Single nucleotide patch base excision repair is the major pathway for removal of thymine glycol from DNA in human cell extracts. J Biol Chem275:11809-13 2000

PubMed ID: 10766805

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

Nouspikel T, Lalle P, Leadon SA, Cooper PK, Clarkson SG, A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: implications for a second XPG function. Proc Natl Acad Sci U S A94:3116-21 1997

PubMed ID: 9096355

Vermeulen W, Jaeken J, Jaspers NG, Bootsma D, Hoeijmakers JH, Xeroderma pigmentosum complementation group G associated with Cockayne syndrome. Am J Hum Genet53:185-92 1993

PubMed ID: 8317483

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