Abstract
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 PTCH1 protein 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 mutations in the PTCH1 gene. 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 PTCH1 protein. Analysis of a high-density single nucleotide polymorphism (SNP) mapping array showed a large ∼1.2-Mb deletion, including the PTCH1 gene in one allele, in a family in which PTCH1 mutations were not identified at the sequence level. These data indicated that all the six families who were diagnosed with BCNS had mutations in the PTCH1 gene and that a single copy of a PTCH1 mutation causes BCNS.
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Acknowledgements
We thank Dr Takada for data management and collection, Ms Iemoto for her technical assistance and the Joint-Use Research facilities at Hyogo College of Medicine. This work was supported by a grant-in-aid from the Project for Frontier of Science from the Ministry of Education, Science, Sports and Culture, Government of Japan.
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Takahashi, C., Kanazawa, N., Yoshikawa, Y. et al. Germline PTCH1 mutations in Japanese basal cell nevus syndrome patients. J Hum Genet 54, 403–408 (2009). https://doi.org/10.1038/jhg.2009.55
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DOI: https://doi.org/10.1038/jhg.2009.55
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