Unexpected phenotype in a frameshift mutation of PTCH1

Area of Science:

• Genetics
• Molecular Biology
• Clinical Medicine

Background:

• Gorlin syndrome (basal cell nevus syndrome) is a rare genetic disorder linked to PTCH1 mutations.
• 9q22.3 microdeletion syndrome shares features with Gorlin syndrome but includes additional symptoms like craniosynostosis and developmental delay.
• Both conditions involve the PTCH1 gene region at 9q22.3.

Observation:

• A case report of an 11-year-old girl with overgrowth, facial dysmorphisms, and craniosynostosis but normal development.
• Initial array-comparative genomic hybridization (aCGH) showed no copy number variations.
• Next-generation sequencing revealed a heterozygous frameshift mutation in the PTCH1 gene.

Findings:

• This is the first reported case of 9q22.3 microdeletion syndrome phenotype resulting from a PTCH1 point mutation.
• The findings underscore the critical role of PTCH1 in the development of metopic craniosynostosis.

Implications:

• This case expands the mutational spectrum for 9q22.3 microdeletion syndrome.
• Further research into PTCH1 function may elucidate its role in craniofacial development and associated disorders.
• Highlights the importance of genetic testing for PTCH1 in patients with overlapping BCNS and 9q22.3 microdeletion syndrome phenotypes.