Abstract
Nevoid basal cell carcinoma syndrome （NBCCS; Gorlin syndrome）, an autosomal dominant disorder caused by mutations in PTCH1, is characterized by minor anomalies and a high incidence of tumors such as basal cell carcinoma（BCC）and medulloblastoma. We have identified PTCH1 mutations in 21 out of 24 cases with NBCCS. More than half of the mutations comprised insertion/deletion of 1–4 nucleotides, resulting in frameshifts in coding. We also found splicing mutations and whole PTCH1 deletions which were intractable to detect with conventional methods. The early genetic testing of suspected cases of NBCCS is advisable in the light of the following reasons: First, many symptoms develop with age, and it is not always easy to diagnose patients at an early age. Second, after radiation therapy for medulloblastoma, NBCCS patients develop secondary cancers in the irradiated areas; therefore, omitting or limiting radiation therapy should be considered. Third, a proper diagnosis with genetic testing helps in the early detection of medulloblastoma and also lessens the risk of developing BCCs by reducing ultraviolet radiation. Finally, emerging small molecule inhibitors of hedgehog signaling may be useful for treating patients with NBCCS-related tumors if potential adverse effects on embryonic and post-natal development are avoided.
