title: Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome.
abstract: We identified seven novel germline mutations of the PTCH gene in eight unrelated Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplified from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations were found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletions, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the strong basic residue arginine was substituted by serine or glycine in highly conserved components of the putative transmembrane domain of PTCH, and these mutations may therefore affect the conformation and function of the PTCH protein. No phenotype-genotype relationships were found in the Japanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian patients.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kobe University, 7 Kusunoki-cho, Shogoin, Chuo-ku, Kobe, 651-0017, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tanioka
authors.forename: Katsu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kawabata
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Murakami
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Iizuka
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D005091:Exons; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface