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A non‐coding mutation in the 5′ untranslated region of patched homologue 1 predisposes to basal cell carcinoma
Author(s) -
Tietze Julia K.,
Pfob Martina,
Eggert Marlene,
Preußen Anna,
Mehraein Yasmin,
Ruzicka Thomas,
Herzinger Thomas
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12267
Subject(s) - patched , coding region , biology , untranslated region , mutation , genetics , germline mutation , three prime untranslated region , basal cell carcinoma , translation (biology) , mutant , cancer research , microbiology and biotechnology , gene , messenger rna , medicine , basal cell , pathology , hedgehog signaling pathway
Mutations in the human homolog of the D rosophila 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.