GM16684
Fibroblast from Skin, Unspecified
Description:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC
XPC COMPLEX SUBUNIT, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPC
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Nucleotide and Nucleic Acid Metabolism |
| Class |
Repair Defective and Chromosomal Instability Syndromes |
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Biopsy Source
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Unspecified
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Cell Type
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Fibroblast
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Tissue Type
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Skin
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Transformant
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Untransformed
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Sample Source
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Fibroblast from Skin, Unspecified
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Race
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White
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Ethnicity
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POLISH/JEWISH
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Clinical summary/Case history
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| PDL at Freeze |
5.59 |
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by LINE assay |
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| 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. |
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| Gene |
XPC |
| Chromosomal Location |
3p25 |
| Allelic Variant 2 |
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. |
| Remarks |
XP12TA; Ashkenazi Jewish; clinically affected; developed skin cancer (basal cell carcinoma) at 2 years of age and died at 10 years of age; 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 sister is GM16685; donor subject is homozygous for a 2 bp deletion in exon 5 of the XPC gene (669_670delAT) resulting in premature termination 10 codons downstream (C223fsX233) |
| Kong YW, Dreaden EC, Morandell S, Zhou W, Dhara SS, Sriram G, Lam FC, Patterson JC, Quadir M, Dinh A, Shopsowitz KE, Varmeh S, Yilmaz ÖH, Lippard SJ, Reinhardt HC, Hemann MT, Hammond PT, Yaffe MB, Enhancing chemotherapy response through augmented synthetic lethality by co-targeting nucleotide excision repair and cell-cycle checkpoints Nature communications11:4124 2018 |
| PubMed ID: 32807787 |
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| 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 cell11:e13010 2018 |
| PubMed ID: 31385397 |
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| Godschalk RW, Ersson C, Riso P, Porrini M, Langie SA, van Schooten FJ, Azqueta A, Collins AR, Jones GD, Kwok RW, Phillips DH, Sozeri O, Allione A, Matullo G, Möller L, Forchhammer L, Loft S, Møller P., DNA-repair measurements by use of the modified comet assay: An inter-laboratory comparison within the European Comet Assay Validation Group (ECVAG). Mutat Res.757(1):60-7 2013 |
| PubMed ID: 23830929 |
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| Wang G, Chuang L, Zhang X, Colton S, Dombkowski A, Reiners J, Diakiw A, Xu XS, The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation. Nucleic Acids Res32(7):2231-40 2004 |
| PubMed ID: 15107491 |
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| 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 |
| Split Ratio |
1:2 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Supplement |
- |
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