title: Nevoid basal cell carcinoma syndrome with cleft lip and palate associated with the novel PTCH gene mutations.
abstract: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities and a predisposition to cancers. Two unrelated patients, 21- and 16-year-old males, with cleft lip and palate and multiple jaw cysts, were diagnosed according to clinical criteria. To confirm a diagnosis of NBCCS, we undertook a molecular genetic analysis of the PTCH gene. Their PTCH genes were analyzed by direct sequencing of the PCR product from their DNA, and previously unreported mutations were identified. A heterozygous duplication at the nucleotide position between 3325 and 3328 of the PTCH gene (c.3325_3328dupGGCG) was detected in the 21-year-old patient. It caused a frameshift mutation, resulting in a premature termination of the PTCH protein. A point mutation (G to C) in intron 7 of the PTCH gene (c.1067+1G>C) was detected in the 16-year-old patient. This caused an aberrant splicing of PTCH. It is interesting to note that the non-canonical cryptic splice-donor site was activated, which did not conform to the GT-AG rule.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tokyo Metropolitan Police Hospital, Tokyo, Japan. sasaki@oms.twmu.ac.jp
authors.forename: Ryo
authors.initials: R
authors.lastname: Sasaki
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
authors.forename: Yorikatsu
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Takayama
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.forename: Kaori
authors.initials: K
authors.lastname: Agawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ando
authors.forename: Tanetaka
authors.initials: T
authors.lastname: Akizuki
mesh_terms: D000293:Adolescent; D001478:Basal Cell Nevus Syndrome / Q000150:complications* / Q000235:genetics*; D001483:Base Sequence; D002971:Cleft Lip / Q000150:complications* / Q000235:genetics; D002972:Cleft Palate / Q000150:complications* / Q000235:genetics; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D055815:Young Adult
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface