Novel PTCH1 Mutation Causes Gorlin-Goltz Syndrome

Area of Science:

• Genetics
• Molecular Biology
• Dermatology

Background:

• Gorlin-Goltz syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare genetic disorder.
• GS is characterized by multiple basal cell carcinomas and other developmental abnormalities.
• Mutations in the patched 1 (PTCH1) gene are a primary cause of GS.

Purpose of the Study:

• To investigate the genetic basis and pathogenic mechanisms of Gorlin-Goltz syndrome in a Chinese family.
• To identify novel mutations in the PTCH1 gene associated with GS.
• To understand the functional consequences of identified PTCH1 mutations.

Main Methods:

• Whole-exome sequencing (WES) was employed to analyze the genomes of affected family members.
• Bioinformatic analyses and conformational studies were conducted to assess the impact of mutations.
• Sanger sequencing was used for validation of the identified mutation.

Main Results:

• A novel heterozygous non-frameshift deletion in the PTCH1 gene (c.3512_3526del, p.1171_1176del) was identified.
• The identified PTCH1 mutation was confirmed through Sanger sequencing.
• Bioinformatic and conformational analyses indicated that the mutation alters PTCH1 protein structure and may lead to functional abnormalities.

Conclusions:

• This study expands the known spectrum of PTCH1 mutations associated with Gorlin-Goltz syndrome.
• The identified PTCH1 mutation (c.3512_3526del) is likely responsible for the GS phenotype in this family due to structural and functional protein changes.
• Findings facilitate earlier diagnosis and screening for GS in affected families.