GM02449

GM02449 LCL from B-Lymphocyte

Description:

XERODERMA PIGMENTOSUM, VARIANT TYPE; XPV
POLYMERASE, DNA, ETA; POLH

Affected:

Yes

Sex:

Male

Age:

30 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

White

Relation to Proband

proband

Confirmation

Clinical summary/Case history

ISCN

46,XY

Species

Homo sapiens

Common Name

Human

Remarks

XPPHBE; variant type; 46,XY; 8% of cells show random chromosome loss, 2% show random gain; normal DNA ligase I and II activity; lymphoblasts synthesize low molecular weight DNA after UV exposure; donor subject has one allele with an insertion of G at nucleotide 1078 of the POLH gene (1078insG) resulting in a frameshift terminating at Asn359 (Asn359fs); the second allele is as yet unidentified

Characterizations

DNA LIGASE I AND II

Normal DNA ligase I & II enzyme activities (Willis et al. Proc Natl Acad Sci USA 84:8016-8020,1987).

DNA METHYLATION

Sano et al (Mutation Res 217:141-151,1989) examined DNA methylation in XP cells. 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 culture was 67%.

IDENTIFICATION OF SPECIES OF ORIGIN

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

Gene

POLH

Chromosomal Location

6p21.1-p12

Allelic Variant 1

Asn359fs; XERODERMA PIGMENTOSUM, VARIANT TYPE

Identified Mutation

1078insG

Phenotypic Data

Remarks

Publications

Johnson RE, Kondratick CM, Prakash S, Prakash L, hRAD30 mutations in the variant form of xeroderma pigmentosum. Science285(5425): 1999

PubMed ID: 10398605

O'Driscoll M, Macpherson P, Xu YZ, Karran P, The cytotoxicity of DNA carboxymethylation and methylation by the model carboxymethylating agent azaserine in human cells. Carcinogenesis20:1855-62 1999

PubMed ID: 10469634

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

Vilpo JA, Vilpo LM, Szymkowski DE, O'Donovan A, Wood RD, An XPG DNA repair defect causing mutagen hypersensitivity in mouse leukemia L1210 cells. Mol Cell Biol15:290-7 1995

PubMed ID: 7799936

Clepet C, Schafer AJ, Sinclair AH, Palmer MS, Lovell-Badge R, Goodfellow PN, The human SRY transcript. Hum Mol Genet2:2007-12 1993

PubMed ID: 8111368

Hansson J, Keyse SM, Lindahl T, Wood RD, DNA excision repair in cell extracts from human cell lines exhibiting hypersensitivity to DNA-damaging agents. Cancer Res51:3384-90 1991

PubMed ID: 2054778

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

PubMed ID: 2918867

Willis, Structural alterations of DNA ligase I in Bloom syndrome. Proc Natl Acad Sci USA84:8016 (1987):141-51 1987

PubMed ID: 2918867

Ramsay RG, Chen P, Imray FP, Kidson C, Lavin MF, Hockey A, Familial melanoma associated with dominant ultraviolet radiation sensitivity. Cancer Res42:2909-12 1982

PubMed ID: 7083179

Moshell AN, Tarone RE, Newfield SA, Andrews AD, Robbins JH, A simple and rapid method for evaluating the survival of xeroderma pigmentosum lymphoid lines after irradiation with ultraviolet light. In Vitro17:299-307 1981

PubMed ID: 6263790