Mutation analysis in patients with nonsyndromic tooth agenesis using exome sequencing.

Area of Science:

• Genetics
• Developmental Biology
• Oral Health

Background:

• Tooth agenesis (TA) is a common congenital anomaly with complex genetic underpinnings.
• It can manifest as syndromic or nonsyndromic forms, necessitating genetic investigation.
• Understanding the genetic basis of nonsyndromic TA is crucial for diagnosis and management.

Purpose of the Study:

• To identify pathogenic mutations in patients with nonsyndromic tooth agenesis.
• To analyze the structural and functional characteristics of identified mutants.
• To contribute to the genetic understanding of nonsyndromic TA.

Main Methods:

• Exome sequencing was employed to detect variants in 72 patients from 43 families with nonsyndromic TA.
• Candidate variants were confirmed using Sanger sequencing.
• Bioinformatics and conformational analyses were performed to elucidate pathogenic mechanisms.

Main Results:

• Eight mutations (six novel, two known) were identified in six genes: WNT10A, LRP6, AXIN2, PAX9, MSX1, and PITX2.
• These mutations were found in eight families with nonsyndromic TA.
• Structural and functional analyses indicated that the mutations severely alter protein structures, potentially causing functional deficits.

Conclusions:

• The study expands the spectrum of known mutations associated with nonsyndromic tooth agenesis.
• The findings provide valuable data for genetic counseling of patients and families.
• Further research is needed to explore the pathogenic mechanisms of TA in cases with unidentified causative variants.