Germline PTCH1 mutations in Japanese basal cell nevus syndrome patients

Basal cell nevus syndrome(BCNS or Gorlin syndrome, OMIM: 109400) is a rare autosomal dominant disorder with high penetrance. It is characterized by developmental anomalies and predisposition to tumors (for example, basal cell carcinoma(BCC) and medulloblastoma). PTCH1, the human homolog of the Drosophila patched gene, was identified as a gene responsible for BCNS. The PTCH1protein is a Hedgehog(Hh) protein receptor and is pivotal for early development, stem cell maintenance and/or differentiation. We analyzed the six Japanese families with BCNS and identified six germline mutationsin the PTCH1gene. One family had a nonsense mutation(c.1196G>A), one had a 1-bp deletion (c.2029delA), two had 2-bp deletions (c.239_240delGA and c.1670_1671delCA) and one had a 58-bp duplication (c.1138_1195dup). They caused premature termination, resulting in the truncation of the PTCH1protein. Analysis of a high-density single nucleotide polymorphism (SNP) mapping array showed a large ~1.2-Mb deletion, including the PTCH1gene in one allele, in a family in which PTCH1mutations were not identified at the sequence level. These data indicated that all the six families who were diagnosed with BCNS had mutations in the PTCH1gene and that a single copy of a PTCH1mutation causes BCNS.