title: Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene.
abstract: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene. To date, we have detected 73 mutations in PTCH1 and ten of them (14 %) were suspected splicing mutations. Eight out of the ten mutations were localized near the splice donor site. Five mutations were localized within the invariant GT-AG splice site, whereas the other five mutations occurred outside the invariant GT-AG site including the last exonic nucleotide. When the transcripts were examined, all mutations resulted in aberrant splicing, including exon skipping or the activation of cryptic splice sites. This is the first extensive report of NBCCS focusing on splice site mutations, and it highlights the importance of analyzing transcripts especially for mutations lying outside the GT-AG splicing consensus site. In addition, the splice site score calculated by Splice-Site Analyzer Tool provided by Tel Aviv University helped predict aberrant splice patterns in most of the cases.
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors: Chise
authors: C
authors: Kato
authors: Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.
authors: Kentaro
authors: K
authors: Fujii
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.
authors: Yuto
authors: Y
authors: Arai
authors: Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.
authors: Hiromi
authors: H
authors: Hatsuse
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.
authors: Kazuaki
authors: K
authors: Nagao
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.
authors: Yoshinaga
authors: Y
authors: Takayama
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan.|Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.
authors: Kouzou
authors: K
authors: Kameyama
authors: Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Katsunori
authors: K
authors: Fujii
authors: Department of Molecular Genetics, Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan. tmiyashi@med.kitasato-u.ac.jp.|Department of Molecular Genetics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan. tmiyashi@med.kitasato-u.ac.jp.
authors: Toshiyuki
authors: 0000-0002-0929-4629
authors: T
authors: Miyashita
mesh_terms: D000293:Adolescent; D000328:Adult; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000072081:Patched-1 Receptor / Q000235:genetics*; D010375:Pedigree; D022821:RNA Splice Sites; D012326:RNA Splicing
chemical_list: C000606236:PTCH1 protein, human; D000072081:Patched-1 Receptor; D022821:RNA Splice Sites
keywords: Nevoid basal cell carcinoma syndrome; PTCH1; Splicing mutation