Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum.
Four mutations of the XPAC gene were identified as molecular bases of different UV-sensitive subgroups of xeroderma pigmentosum (XP) group A. One was a G to C transversion at the last nucleotide of exon 4 in GM1630/GM2062, a little less hypersensitive subgroup than the most sensitive XP2OS/XP12RO. The second mutation was a G to A transition at the last nucleotide of exon 3 in GM2033/GM2090, an intermediate subgroup. Both mutations caused almost complete inactivation of the canonical 5' splice donor site and aberrant RNA splicing. The third mutation was a nucleotide transition altering the Arg-211 codon (CGA) to a nonsense codon (TGA) in another allele of GM2062. The fourth mutation was a nucleotide transversion altering the His-244 codon (CAT) to an Arg codon (CGT) in XP8LO, an intermediate subgroup. Our results strongly suggest that the clinical heterogeneity in XP-A is due to different mutations in the XPAC gene.
Institute for Molecular and Cellular Biology, Osaka University, Japan.
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Satokata
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Tanaka
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Yuba
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Okada
D000293:Adolescent; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D004247:DNA / Q000528:radiation effects; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics; D005091:Exons; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D004247:DNA