Potential hot spot for de novo mutations in PTCH1 gene in Gorlin syndrome patients: a case report of twins from Croatia

Croat Med J. 2018 Feb 28;59(1):20-24. doi: 10.3325/cmj.2018.59.20.


We describe a case of twins with sporadic Gorlin syndrome. Both twins had common Gorlin syndrome features including calcification of the falx cerebri, multiple jaw keratocysts, and multiple basal cell carcinomas, but with different expressivity. One brother also had benign testicular mesothelioma. We propose this tumor type as a possible new feature of Gorlin syndrome. Gorlin syndrome is a rare autosomal dominant disorder characterized by both developmental abnormalities and cancer predisposition, with variable expression of various developmental abnormalities and different types of tumors. The syndrome is primarily caused by mutations in the Patched 1 (PTCH1) gene, although rare mutations of Patched 2 (PTCH2) or Suppressor of Fused (SUFU) genes have also been found. Neither founder mutations nor hot spot locations have been described for PTCH1 in Gorlin syndrome patients. Although de novo mutations of the PTCH1 gene occur in almost 50% of Gorlin syndrome cases, there are a few recurrent mutations. Our twin patients were carriers of a de novo mutation in the PTCH1 gene, c.3364_3365delAT (p.Met1122ValfsX22). This is, to our knowledge, the first Gorlin syndrome-causing mutation that has been reported four independent times in distant geographical locations. Therefore, we propose the location of the described mutation as a potential hot spot for mutations in PTCH1.

Publication types

  • Case Reports
  • Twin Study

MeSH terms

  • Adult
  • Basal Cell Nevus Syndrome / genetics*
  • Base Sequence
  • Diseases in Twins / genetics*
  • Genetic Linkage
  • Humans
  • Male
  • Mutation*
  • Patched-1 Receptor / genetics*
  • Polymorphism, Single Nucleotide
  • Skin Neoplasms / genetics*
  • Twins, Monozygotic / genetics*


  • PTCH1 protein, human
  • Patched-1 Receptor