NA04314
DNA from Fibroblast
Description:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP A; XPA
XPA, DNA DAMAGE RECOGNITION AND REPAIR FACTOR; XPA
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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 |
| Quantity |
10 µg |
| Quantitation Method |
Please see our FAQ |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Sample Source
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DNA from Fibroblast
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Race
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Asian
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Ethnicity
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JAPANESE
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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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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase, Glucose-6-Phosphate Dehydrogenase, and Lactate Dehydrogenase Isoenzyme Electrophoresis |
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| Gene |
XPA |
| Chromosomal Location |
9q22.3-q31 |
| Allelic Variant 1 |
278700.0001; XERODERMA PIGMENTOSUM, TYPE A |
| Identified Mutation |
3-PRIME SPLICE SITE, INTRON 3; Tanaka et al. [Nature 348: 73-76 (1990)] found that most Japanese patients with type A xeroderma pigmentosum had a G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPAC gene. Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912, (1990)] found that the single base substitution abolished the canonical 3-prime splice site and created 2 abnormally spliced mRNA forms. The larger form was identical with normal mRNA except for a dinucleotide deletion at the 5-prime end of exon 4. This deletion resulted in a frameshift with premature termination of translation in exon 4. The smaller form had a deletion of the entire exon 3 and the dinucleotide at the 5-prime end of exon 4. A single base substitution creates a new cleavage site for the restriction endonuclease AlwNI. Using the AlwNI RFLP, Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912 (1990)] found that 16 of 21 unrelated Japanese patients with XP were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 blacks with group A XP did not have this mutant allele. Kore-eda et al. [Arch. Derm. 128: 971-974 (1992)] demonstrated the usefulness of the polymerase chain reaction (PCR) followed by search for the AlwNI RFLP in the diagnosis of XPA. Cleaver et al. [Hum. Molec. Genet. 4: 1685-1687 (1995)] stated that homozygosity for a G-to-C transversion at the 3-prime acceptor site of intron III/exon IV represents 80 to 90% of Japanese patients with XPA. |
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| Gene |
XPA |
| Chromosomal Location |
9q22.3-q31 |
| Allelic Variant 2 |
278700.0001; XERODERMA PIGMENTOSUM, TYPE A |
| Identified Mutation |
3-PRIME SPLICE SITE, INTRON 3; Tanaka et al. [Nature 348: 73-76 (1990)] found that most Japanese patients with type A xeroderma pigmentosum had a G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPAC gene. Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912, (1990)] found that the single base substitution abolished the canonical 3-prime splice site and created 2 abnormally spliced mRNA forms. The larger form was identical with normal mRNA except for a dinucleotide deletion at the 5-prime end of exon 4. This deletion resulted in a frameshift with premature termination of translation in exon 4. The smaller form had a deletion of the entire exon 3 and the dinucleotide at the 5-prime end of exon 4. A single base substitution creates a new cleavage site for the restriction endonuclease AlwNI. Using the AlwNI RFLP, Satokata et al. [Proc. Nat. Acad. Sci. 87: 9908-9912 (1990)] found that 16 of 21 unrelated Japanese patients with XP were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 blacks with group A XP did not have this mutant allele. Kore-eda et al. [Arch. Derm. 128: 971-974 (1992)] demonstrated the usefulness of the polymerase chain reaction (PCR) followed by search for the AlwNI RFLP in the diagnosis of XPA. Cleaver et al. [Hum. Molec. Genet. 4: 1685-1687 (1995)] stated that homozygosity for a G-to-C transversion at the 3-prime acceptor site of intron III/exon IV represents 80 to 90% of Japanese patients with XPA. |
| Remarks |
Japanese; XP30S; severe XP; mental retardation; gait disturbance; less than 2% of normal post UV unscheduled DNA synthesis; passage 10 at CCR; slow growing culture; affected sister is GM02345; donor subject is homozygous for the G-to-C transversion at the 3-prime splice acceptor site of intron 3 of the XPA gene, abolishing the canonical 3-prime splice site and creating two abnormally spliced mRNA forms. |
| States JC, McDuffie ER, Myrand SP, McDowell M, Cleaver JE, Distribution of mutations in the human xeroderma pigmentosum group A gene and their relationships to the functional regions of the DNA damage recognition protein. Hum Mutat12:103-13 1998 |
| PubMed ID: 9671271 |
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| Satokata I, Tanaka K, Miura N, Narita M, Mimaki T, Satoh Y, Kondo S, Okada Y, Three nonsense mutations responsible for group A xeroderma pigmentosum. Mutat Res273:193-202 1992 |
| PubMed ID: 1372102 |
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| Takebe H, Miki Y, Kozuka T, Furuyama JI, Tanaka K, DNA repair characteristics and skin cancers of xeroderma pigmentosum patients in Japan. Cancer Res37:490-5 1977 |
| PubMed ID: 832273 |
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