title: Gene alterations and clinical characteristics of xeroderma pigmentosum group A patients in Japan.
abstract: METHODS
  The responsible gene for xeroderma pigmentosum group A was recently identified. This study was performed to detect the gene alteration of xeroderma pigmentosum group A complementing gene in 29 xeroderma pigmentosum group A patients in Japan and to analyze whether genetic alterations in the xeroderma pigmentosum group A complementing gene are related to the clinical features.
  
  
  RESULTS
  Of 29 patients, 25 (86%) had a mutation at the splicing junction of intron 3 and exon 4 in the homozygous state that was detected by the polymerase chain reaction and the AlwN I-restriction fragment length polymorphism. Patients having a splicing mutation at intron 3 in the homozygous state develop severe skin manifestations from early infancy and severe progressive neurologic abnormalities, including sensorineural hearing impairment, brain atrophy, mental retardation, areflexia, and ataxia. Four patients were heterozygous for splicing mutation in intron 3. Among them, at least three patients showed milder skin symptoms and milder neurologic abnormalities than patients with the homozygous splicing mutation. Two patients (single-ovum twins) revealed a compound heterozygote of splicing mutation of intron 3 and a nonsense mutation of exon 6. One patient had the splicing mutation and another mutation at the last codon of exon 5, a type of mutation that has never been reported.
  
  
  CONCLUSIONS
  These data indicate that different genetic alterations in the xeroderma pigmentosum group A complementing gene may induce different clinical features.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Kyoto University, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nishigori
authors.forename: S
authors.initials: S
authors.lastname: Moriwaki
authors.forename: H
authors.initials: H
authors.lastname: Takebe
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Imamura
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3; D002894:Chromosomes, Human, Pair 4; D004260:DNA Repair; D005260:Female; D005816:Genetic Complementation Test; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014983:Xeroderma Pigmentosum / Q000235:genetics*