title: XPA gene mutations resulting in subtle truncation of protein in xeroderma pigmentosum group A patients with mild skin symptoms.
abstract: Comparisons of the clinical manifestations with gene mutations in patients with xeroderma pigmentosum group A (XPA) have suggested that those with mutations closer to the C-terminal coding region of the XPA gene have milder neurological and cutaneous symptoms. Here we report on four middle-aged, newly diagnosed Japanese XPA patients whose unusually mild symptoms, especially those affecting the skin, implicate a reduced association of a subtle defect in the C-terminus of XPA protein with skin lesions. All patients had a heterozygous G → C transversion at the splice acceptor site of XPA intron 3. We identified previously unreported heterozygous mutations in exon 6: a single-base insertion (690insT) in one patient and a four-base insertion (779insTT and 780insTT) in the other patients. These mutations led to the frameshift that created new premature termination codons, resulting in the production of truncated XPA proteins. They were longer than any previously reported truncated XPA protein, suggesting that the minimal cutaneous symptoms in these patients are due to a higher residual level of XPA protein activity and that the subtle defect in the C-terminus of XPA protein is more closely related to neurological impairment than to cutaneous abnormalities.
authors.affiliation: Innovative Beauty Science Laboratory, Kanebo Cosmetics, Odawara, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Endo
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Shintaro
authors.initials: S
authors.lastname: Inoue
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iijima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuru
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Moriwaki
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D017434:Protein Structure, Tertiary / Q000235:genetics; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology*; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology*; D051760:Xeroderma Pigmentosum Group A Protein / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; C497314:XPA protein, human; D051760:Xeroderma Pigmentosum Group A Protein