Nonsyndromic craniosynostosis: novel coding variants.

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Craniosynostosis (CS) is the premature fusion of neurocranial sutures, associated with ~200 syndromes.
• However, 65-85% of CS patients lack other major birth defects, indicating a role for genetic factors in isolated CS.

Purpose of the Study:

• To investigate the genetic basis of isolated nonsyndromic craniosynostosis (NCS).
• To identify novel pathogenic variants in genes associated with syndromic CS that may contribute to NCS.

Main Methods:

• Targeted next-generation sequencing of 60 candidate genes was performed.
• Patients with sagittal NCS (sNCS, n=40) and coronal NCS (cNCS, n=19) were analyzed.

Main Results:

• Eighteen known and five novel pathogenic variants were identified, including three de novo variants.
• A novel BBS9 variant was found in a cNCS patient; BBS9 is crucial for ciliogenesis in suture development.
• Variants in EFNB1 and TWIST1, genes linked to syndromic CS, were also identified in cNCS patients.

Conclusions:

• Genetic variants in syndromic CS genes contribute to isolated CS, supporting their inclusion in genetic screening panels.
• The novel BBS9 variant highlights its potential role in the pathogenesis of craniosynostosis.