GM16685
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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2
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Relation to Proband
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sister
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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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| 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 |
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). |
| 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 |
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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 |
1:5 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
20% fetal bovine serum Not inactivated |
| Substrate |
None specified |
| Subcultivation Method |
trypsin-EDTA |
| Supplement |
- |
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