GM16685

GM16685 Fibroblast from Skin, Unspecified

Description:

XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC
XPC COMPLEX SUBUNIT, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPC

Affected:

Yes

Sex:

Female

Age:

3 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

Biopsy Source

Unspecified

Cell Type

Fibroblast

Tissue Type

Skin

Transformant

Untransformed

Sample Source

Fibroblast from Skin, Unspecified

Race

White

Ethnicity

POLISH/JEWISH

Family Member

Relation to Proband

sister

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

XP25TA; Ashkenazi Jewish; clinically affected; sun protected; developed skin cancer at 10 years of age; by age 24, donor subject had developed 10 skin neoplasms (five basal cell carcinomas, two squamous cell carcinomas, and three melanomas); skin fibroblasts showed reductions in post-ultraviolet survival (11% of normal), unscheduled DNA synthesis (10% of normal), global genome DNA repair (15% of normal); and plasmid host cell reactivation (5% of normal); affected brother is GM16684; donor subject is homozygous for a 2 base pair deletion in exon 5 (del AT669_670) of the XPC gene, which results in a new termination site 10 codons downstream, as well as a functional polymorphic transversion in exon 15 (2920A>C).

Characterizations

Gene

XPC

Chromosomal Location

3p25

Allelic Variant 1

613208.0006; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

2-BP DEL, 669AT; Slor et al. [J. Invest. Derm. 115: 974-980 (2000)] reported a homozygous A-T deletion of 2 bases (669-670) in exon 5 of the XPC gene in two Israeli sibs with severe xeroderma pigmentosum symptoms. The mutation, which was expected to encode a truncated xeroderma pigmentosumcomplementation group C protein, resulted in a new termination site 10 codons downstream. Cultured skin fibroblasts from both patients showed reductions in postultraviolet survival (11% of normal), unscheduled DNA synthesis (10% of normal), global genome DNA repair (15% of normal), and plasmid host cell reactivation (5% of normal). Transcription-coupled DNA repair was normal, however. Northern blot analysis revealed greatly reduced xeroderma pigmentosum complementation group C mRNA. Sun protection delayed the onset of skin cancer and prolonged life in the second sib.

Gene

XPC

Chromosomal Location

3p25

Allelic Variant 2

613208.0006; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

Phenotypic Data

Remarks

Publications

Narisu N, Rothwell R, Vrtacnik P, Rodríguez S, Didion J, Zöllner S, Erdos MR, Collins FS, Eriksson M, Analysis of somatic mutations identifies signs of selection during in vitro aging of primary dermal fibroblasts Aging cell:e13010 2018

PubMed ID: 31385397

Slor H, Batko S, Khan SG, Sobe T, Emmert S, Khadavi A, Frumkin A, Busch DB, Albert RB, Kraemer KH, Clinical, cellular, and molecular features of an Israeli xeroderma pigmentosum family with a frameshift mutation in the XPC gene: sun protection prolongs life. J Invest Dermatol115(6):974-80 2000

PubMed ID: 11121128