Detection of large deletion of 4.5 Mb in PTCH region in a Croatian Gorlin syndrome sace by semi-quantitative fluorescent multiplex PCR

Gorlin syndrome or Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is a rare autosomal dominant disorder characterized by developmental abnormalities, cysts of the skin, jaws, and mesentery and cancer predisposition to basal cell carcinomas (BCC), medulloblastomas, meningiomas, fibromas of the ovaries and heart. The syndrome is caused by mutations in the human homolog of the Drosophila patched gene, PTCH. PTCH is a tumor supressor gene, located at 9q22.3, and encodes a 12 transmembrane glycoprotein that acts as an antagonist in the Hedgehog signaling pathway. We present a Gorlin syndrome patient with typical phenothypical features of widespread basal cell carcinomas, jaw malformations, strabismus and mental retardation, with family history that beside basal cell carcinomas includes lung cancer and gastrointestinal carcinomas. Since we found no mutations in exons of PTCH gene with conventional methods of SSCP, dHPLC screening and direct sequencing, we developed a new method of semi-quantitative fluorescent multiplex PCR with polymorphic markers surrounding PTCH gene. With this method we defined a deletion of 4.5 Mb in size between markers SHGC- 110746 and SHGC-132418 (9q22.3-9q31.1).Those results confirm previously reported findings that large deletions in PTCH region may also cause Gorlin syndrome through haploinsuficiency of PTCH gene.