engleski

Large deletions in 9q22.21-9q22.33 region of Gorlin syndrome patients

Gorlin syndrome, also known as Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Basal Cell Nevus Syndrome (BCNS), is an autosomal dominant disorder that is characterized by various developmental abnormalities, like cysts of the skin, jaw cysts, bone malformations and different tumors like basal cell carcinomas (BCC) as most frequent, and also medulloblastomas, meningiomas, fibromas of the ovaries and heart. The prevalence is estimated at one per 57000. Phenotypical and genotypical diversity in Gorlin syndrome is referring to inactivating mutations in only one gene, PTCH, the human homologue of the Drosophila segment-polarity gene patched. PTCH is a tumor suppressor gene, located at 9q22.3, encoding a 12-pass transmembrane glycoprotein that acts as an antagonist in the Hedgehog signaling pathway. The 34 kb gene contains 23 exons and there are several hundred mutations, spanning the whole gene. Although there are some recurring mutations, there are no apparent hot spots. Nonsense, frameshift, in-frame deletions, splicesite, and missense mutations all have been described in the Gorlin syndrome patients. In some cases large deletions in PTCH region have been reported. We developed semi-quantitative fluorescent multiplex PCR with polymorphic markers surrounding PTCH and analyzed the whole 9q22 region in 50 Gorlin syndrome cases from France and Croatia. In three cases we found large deletions from 4-7 megabases in length, giving some depth and additional indications for phenotype diversity of the Gorlin syndrome.

Gorlin syndrome ; PTCH ; large deletions

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