A non-coding mutation in the 5′ untranslated region of patched homologue 1 predisposes to basal cell carcinoma

• Published in: Experimental dermatology Vol. 22; no. 12; pp. 834 - 835
• Main Authors: Tietze, Julia K., Pfob, Martina, Eggert, Marlene, von Preußen, Anna, Mehraein, Yasmin, Ruzicka, Thomas, Herzinger, Thomas
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.12.2013
• Subjects: 5' untranslated region; 5' Untranslated Regions; Adult; Aged; basalcellcarcinoma; Base Sequence; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - metabolism; Exons; Female; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Male; Molecular Sequence Data; Mutation; patched homologue 1-mutation; Patched Receptors; Patched-1 Receptor; Protein Biosynthesis; Receptors, Cell Surface - genetics; RNA, Untranslated; Signal Transduction; Skin Neoplasms - genetics; Skin Neoplasms - metabolism; patched homologue 1-mutation; basalcellcarcinoma; 5’ untranslated region
• ISSN: 0906-6705; 1600-0625; 1600-0625
• DOI: 10.1111/exd.12267

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.