title: A non-coding mutation in the 5' untranslated region of patched homologue 1 predisposes to basal cell carcinoma.
abstract: Mutations in the human homolog of the Drosophila patched gene, patched homologue 1 (PTCH-1), are responsible for most hereditary and sporadic basal cell carcinomas. Here, we present a father and daughter with a high propensity for the development of basal cell carcinoma who were heterozygous for a non-coding germline mutation in the 5' untranslated region (UTR) of PTCH-1 (insertion of a surplus CGG triplet at the site of a seven times CGG repeat). We analysed the impact of this mutation on PTCH translation using a luciferase-based reporter vector. Insertion of an eighth CGG in the 5' UTR repressed protein translation dramatically when compared to the wild-type sequence. Our results suggest that this non-coding variant in the 5' UTR represents a mutation predisposing to basal cell carcinoma.
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tietze
authors.forename: Martina
authors.initials: M
authors.lastname: Pfob
authors.forename: Marlene
authors.initials: M
authors.lastname: Eggert
authors.forename: Anna
authors.initials: A
authors.lastname: von Preußen
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Mehraein
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Thomas
authors.initials: T
authors.lastname: Herzinger
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D014176:Protein Biosynthesis; D022661:RNA, Untranslated; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D022661:RNA, Untranslated; D011956:Receptors, Cell Surface
keywords: 5’ untranslated region; basalcellcarcinoma; patched homologue 1-mutation