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 |
| Alternate IDs |
GM17090 [XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C; XPC] |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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Asian
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Ethnicity
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KOREAN
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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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| 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 |
XPC |
| Chromosomal Location |
3p25 |
| Allelic Variant 1 |
613208.0005; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C, WITH AUTISM AND HYPOGLYCINEMIA |
| Identified Mutation |
IVS9DS, T>G, +2; Khan et al. [J. Invest. Derm. 111: 791-796 (1998)] found a T-to-G transversion at the splice donor site of XPC exon 9 in a 4-year-old boy of Korean ancestry who had xeroderma pigmentosum with sun sensitivity, multiple cutaneous neoplasms, and inability to speak. Neurologic examination showed hyperactivity and autistic features without typical XP neurologic abnormalities. Complementation studies assigned this case to XP group C. A markedly reduced level of XPC mRNA was found. Two XPC cDNA bands were identified. One band had a deletion of 161 bases comprising the entire exon 9, which resulted in premature termination of the mutant XPC mRNA. The larger band also had the same deletion of exon 9 but, in addition, had an insertion of 155 bases in its place (exon 9a), resulting in an in-frame XPC mRNA. The 155-bp XPC exon 9a insertion was located in intron 9 and was flanked by strong splice donor and acceptor sequences. Analysis of the patient's blood showed persistently low levels of glycine (68 microM; normal = 125-318 microM). Normal glycine levels were maintained with oral glycine supplements, and the patient's hyperactivity diminished. |
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| Gene |
XPC |
| Chromosomal Location |
3p25 |
| Allelic Variant 2 |
613208.0005; XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP C, WITH AUTISM AND HYPOGLYCINEMIA |
| Identified Mutation |
IVS9DS, T>G, +2; Khan et al. [J. Invest. Derm. 111: 791-796 (1998)] found a T-to-G transversion at the splice donor site of XPC exon 9 in a 4-year-old boy of Korean ancestry who had xeroderma pigmentosum with sun sensitivity, multiple cutaneous neoplasms, and inability to speak. Neurologic examination showed hyperactivity and autistic features without typical XP neurologic abnormalities. Complementation studies assigned this case to XP group C. A markedly reduced level of XPC mRNA was found. Two XPC cDNA bands were identified. One band had a deletion of 161 bases comprising the entire exon 9, which resulted in premature termination of the mutant XPC mRNA. The larger band also had the same deletion of exon 9 but, in addition, had an insertion of 155 bases in its place (exon 9a), resulting in an in-frame XPC mRNA. The 155-bp XPC exon 9a insertion was located in intron 9 and was flanked by strong splice donor and acceptor sequences. Analysis of the patient's blood showed persistently low levels of glycine (68 microM; normal = 125-318 microM). Normal glycine levels were maintained with oral glycine supplements, and the patient's hyperactivity diminished. |
| Remarks |
XP22BE; Korean; skin lesions including squamous cell carcinoma and melanomas; mild developmental & significant speech delays; growth below the fifth percentile; hyperactivity with delayed motor development and absent speech; persistent low levels of glycine in the blood; increased levels of valine, isoleucine, leucine, methionine, and tyrosine in the blood and urine; the donor subject is homozygous for a T>G transversion in the splice donor site of exon 9 in the XPC gene (IVS9+2T>G) which results in three different mRNA isoforms: isoform I has a loss of exon 9, isoform II has an insertion of exons 9b and 9a, and isoform III has a deletion of exon 9 and an insertion of exon 9a. |
| Khan SG, Levy HL, Legerski R, Quackenbush E, Reardon JT, Emmert S, Sancar A, Li L, Schneider TD, Cleaver JE, Kraemer KH, Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia. J Invest Dermatol111(5):791-6 1998 |
| PubMed ID: 9804340 |
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