title: Aberrant splicing and truncated-protein expression due to a newly identified XPA gene mutation.
abstract: A group A xeroderma pigmentosum (XPA) patient, XP2NI, is a compound heterozygote with a newly identified G to C transversion at the last nucleotide in exon 5 in one chromosome, and with the known splicing mutation in intron 3 in another chromosome in the XPA gene. XP2NI had mild skin symptoms and the cells were slightly less sensitive to UV radiation than the cells of typical severe XPA patients who have the splicing mutation in intron 3 homozygously. Reverse transcriptase (RT)-PCR and sequencing of the PCR products revealed that the mutation in exon 5 resulted in producing three types of aberrant mRNA, lacking 7 nucleotides at the end of exon 5, lacking entire exon 5, and lacking exons 3, 4 and 5. A significant amount of a truncated type of protein was produced in XP2NI cells, and the size of the protein indicated that it should have been translated from the mRNA, lacking the 7 nucleotides and retained one of the zinc-finger domains required for the DNA repair activity. The clinical mildness of XP2NI may be due to the residual DNA repair activity of the truncated XPA protein, while no XPA protein was detected in the XPA cells with the homozygous intron 3 splicing mutation.
authors.affiliation: Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: C
authors.initials: C
authors.lastname: Nishigori
authors.forename: T
authors.initials: T
authors.lastname: Yagi
authors.forename: H
authors.initials: H
authors.lastname: Takebe
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured / Q000528:radiation effects; D002648:Child; D004247:DNA / Q000528:radiation effects; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D017384:Sequence Deletion; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000378:metabolism; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein; D004247:DNA