Gorlin syndrome with an ovarian leiomyoma associated with a PTCH1 second hit

Am J Med Genet A. 2016 Apr;170A(4):1029-34. doi: 10.1002/ajmg.a.37517. Epub 2016 Jan 18.


We describe a Gorlin syndrome (GS) case with two different second hit mutations of PTCH1, one in a keratocystic odontogenic tumor (KCOT) and the other in an ovarian leiomyoma. GS is a rare genetic condition manifesting as multiple basal cell nevi associated with other features such as medulloblastomas, skeletal abnormalities, and ovarian fibromas. A 21-year-old Japanese woman with a history of two KCOTs was diagnosed with GS according to clinical criteria. A PTCH1 mutation, c.1427del T, was detected in peripheral blood. A novel PTCH1 mutation, c.264_265insAATA, had been found in the maxillary KCOT as a second hit mutation. More recently, the ovarian tumor was detected during a gynecological examination. Laparoscopic adnexectomy was performed, and the pathological diagnosis of the ovarian tumor was leiomyoma. Interestingly, another novel mutation, loss of heterozygosity spanning from 9q22.32 to 9q31.2, including PTCH1 and 89 other genes, was detected in this ovarian tumor, providing evidence of a second hit mutation. This is the first report describing a GS-associated ovarian tumor carrying a second hit in the PTCH1 region. We anticipate that accumulation of more cases will clarify the importance of second hit mutations in ovarian tumor formation in GS.

Keywords: Gorlin syndrome; LOH; PTCH1 second hit; leiomyoma; ovarian tumor.

Publication types

  • Case Reports

MeSH terms

  • Basal Cell Nevus Syndrome / complications*
  • Basal Cell Nevus Syndrome / diagnosis
  • Basal Cell Nevus Syndrome / genetics*
  • Chromosomes, Human, Pair 9
  • Comparative Genomic Hybridization
  • DNA Mutational Analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Leiomyoma / complications*
  • Leiomyoma / diagnosis
  • Leiomyoma / genetics*
  • Leiomyoma / surgery
  • Magnetic Resonance Imaging
  • Mutation
  • Ovarian Neoplasms / complications*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / surgery
  • Patched-1 Receptor / genetics*
  • Young Adult


  • Patched-1 Receptor