GM02634

GM02634 LCL from B-Lymphocyte

Description:

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

Affected:

Yes

Sex:

Female

Age:

16 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

Peripheral vein

Cell Type

B-Lymphocyte

Tissue Type

Blood

Transformant

Epstein-Barr Virus

Sample Source

LCL from B-Lymphocyte

Race

Black/African American

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

De Sanctis-Cacchione; lupus erythematosus; XP1MI; low level of UV induced unscheduled DNA synthesis in fibroblasts; see GM02096 (fibroblast); XP-associated neurologic abnormalities, a rarity in group C; the donor subject carries a point mutation that converts the proline at position 218 to histidine [Pro218His (P218H)]. The cell line is either homozygous or hemizygous for this mutation.

Characterizations

IDENTIFICATION OF SPECIES OF ORIGIN

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

DNA METHYLATION

Sano et al (Mutation Res 217:141-151,1989) examined DNA methylation in normal and Xeroderma pigmentosum cell lines. The amount of 5-methylcytosine in DNA from XP cell lines was on average about 70% of that in DNA from normal controls. The value observed for this XP cell line was 94%. Southern hybridization analysis showed that the HLA-DRa gene in XP B-lymphoblasts was differently methylated from normals, but its expression was apparently unaffected. The methylation of dihydrofolate reductase, a housekeeping gene, was the same as in controls.

Gene

XPC

Chromosomal Location

3p25

Allelic Variant 1

613208.0001; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C

Identified Mutation

PRO218HIS; In cell line XP1MI, Li et al. [Nature Genet. 5: 413-417, (1993)] found, by complete sequencing of the 2,472 bp coding sequence of the XPC gene, a point mutation that converted proline at position 218 to histidine. The finding suggested that the cell line was either homozygous or hemizygous for this mutation. The XP1MI cell line was the most UV-sensitive of the five cell lines analyzed by Li et al. [Nature Genet. 5: 413-417, (1993)]. Furthermore, the patient demonstrated XP-associated neurologic abnormalities, a rarity in group C.

Phenotypic Data

Remarks

Publications

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

Gunz D, Hess MT, Naegeli H, Recognition of DNA adducts by human nucleotide excision repair. Evidence for a thermodynamic probing mechanism. J Biol Chem271:25089-98 1996

PubMed ID: 8810263

Reardon JT, Mu D, Sancar A, Overproduction, purification, and characterization of the XPC subunit of the human DNA repair excision nuclease. J Biol Chem271:19451-6 1996

PubMed ID: 8702634

Li L, Bales ES, Peterson CA, Legerski RJ, Characterization of molecular defects in xeroderma pigmentosum group C. Nat Genet5(4):413-7 1993

PubMed ID: 8298653

Zhukovskaya N, Rydberg B, Karran P, Inactive O6-methylguanine-DNA methyltransferase in human cells. Nucleic Acids Res20:6081-90 1992

PubMed ID: 1461738

Sano H, Shiomi N, Imanishi K, Maie O, Shiomi T, DNA methylation in xeroderma pigmentosum. Mutat Res217:141-51 1989

PubMed ID: 2918867

Hananian J, Cleaver JE, Xeroderma pigmentosum exhibiting neurological disorders and systemic lupus erythematosus. Clin Genet17:39-45 1980

PubMed ID: 7389185