Unexpected phenotype in a frameshift mutation of PTCH1

Mol Genet Genomic Med. 2020 Jan;8(1):e987. doi: 10.1002/mgg3.987. Epub 2019 Oct 2.


Background: Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), is a rare autosomal dominant genetic condition, characterized by the presence of multiple basal cell carcinomas at a young age, odontogenic keratocysts, skeletal anomalies, macrocephaly, and dysmorphisms. BCNS is mainly caused by mutations in PTCH1, an onco-suppressor gene that maps at 9q22.3 region. A disease related to BCNS is the 9q22.3 microdeletion syndrome. This condition has an overlapping clinical phenotype with the BCNS, but it can present in addition: metopic craniosynostosis, overgrowth, obstructive hydrocephalus, developmental delay, intellectual disability, and seizures. This syndrome is caused by the deletion of a genomic region containing the PTCH1 and the FANCC.

Methods and results: We report the case of an 11-year-old girl that came to our attention for overgrowth, dysmorphic features of the face, and craniosynostosis, but with a normal intellectual and motor development. At first we performed an array-comparative genomic hybridization (aCGH) analysis. The analysis showed no copy number changes. Then, we performed the analysis of the PTCH1 by next-generation sequencing. This analysis showed a heterozygous frameshift mutation.

Conclusion: This is the first case with a PTCH1 point mutation with a 9q22.3 microdeletion syndrome phenotype. This finding may strengthen the importance of the role of the PTCH1, especially regarding the metopic craniosynostosis.

Keywords: 9q22.3 microdeletion syndrome; Gorlin syndrome; PTCH1; craniosynostosis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basal Cell Nevus Syndrome / genetics*
  • Basal Cell Nevus Syndrome / pathology
  • Child
  • Female
  • Frameshift Mutation*
  • Heterozygote
  • Humans
  • Patched-1 Receptor / genetics*
  • Phenotype*


  • PTCH1 protein, human
  • Patched-1 Receptor