title: Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome.
abstract: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1, encoding a receptor for the secreted protein, sonic hedgehog. Recently, a Chinese family with NBCCS carrying a missense mutation in PTCH2, a close homolog of PTCH1, was reported. However, the pathological significance of missense mutations should be discussed cautiously. Here, we report a 13-year-old girl diagnosed with NBCCS based on multiple keratocystic odontogenic tumors and rib anomalies carrying a frameshift mutation in the PTCH2 gene (c.1172_1173delCT). Considering the deleterious nature of the frameshift mutation, our study further confirmed a causative role for the PTCH2 mutation in NBCCS. The absence of typical phenotypes in this case such as palmar/plantar pits, macrocephaly, falx calcification, hypertelorism and coarse face, together with previously reported cases, suggested that individuals with NBCCS carrying a PTCH2 mutation may have a milder phenotype than those with a PTCH1 mutation.
authors.affiliation: Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, 260-8670, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Maiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hatsuse
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shiohama
authors.forename: Hideki
authors.initials: H
authors.lastname: Uchikawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001478:Basal Cell Nevus Syndrome / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009808:Odontogenic Tumors / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C000606236:PTCH1 protein, human; C000606238:PTCH2 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D000072082:Patched-2 Receptor; D011956:Receptors, Cell Surface