A novel truncating mutation of PTCH1 in a Chinese family with Gorlin syndrome

Gorlin syndrome, a rare autosomal dominant disease, is characterized by numerous basal cell carcinomas, multiple jaw cysts, palmar and plantar pits and embryological deformities. Mutations in the PTCH1 gene are the most common molecular defects associated with Gorlin syndrome. We detected a duplication of thymine after nucleotide position 2927 in exon 18 of the PTCH1 gene (c.2927 dupT) in a fifty-year-old male proband with perianal basal cell carcinoma and his brother. The mutation creates a frameshift and leads to a premature stop codon (p.Tyr977 Leufs* 16) lacking 5 of the 12 transmembrane-spanning domains. However, the functional significance of truncation of the N terminal regions remains currently unknown and to be further investigated. The current findings indicate that genetic testing of PTCH1 gene mutational status may aid in the early diagnosis of Gorlin syndrome in which multiple complex abnormalities are present, hampering prompt diagnosis and treatment.