Novel EDAR mutation in tooth agenesis and variable associated features.

Area of Science:

• Genetics
• Developmental Biology
• Oral Health

Background:

• Tooth agenesis (TA) is a common congenital dental anomaly characterized by the developmental absence of permanent teeth.
• Genetic factors play a significant role in TA, with various genes implicated in tooth development.
• Understanding the genetic basis of TA is crucial for diagnosis and potential therapeutic interventions.

Observation:

• A large Pakistani family presented with autosomal dominant tooth agenesis (TA) with variable expressivity.
• Affected individuals exhibited specific patterns of tooth absence, primarily incisors and canines, with associated dental anomalies like diastema and malocclusion.
• Notably, no signs of ectodermal dysplasia were observed in the affected family members.

Findings:

• Linkage analysis and exome sequencing identified a novel nonsense variant, EDAR c.1302G>A, p.(Trp434*), in affected individuals.
• This variant is predicted to result in a premature termination codon, leading to the deletion of C-terminal residues of the EDAR protein.
• This is the largest reported family with EDAR-related TA, demonstrating a highly variable phenotype without ectodermal dysplasia.

Implications:

• The identification of a novel EDAR variant expands the spectrum of mutations associated with nonsyndromic tooth agenesis.
• This research underscores the critical role of the EDAR gene in human tooth development and highlights its potential for causing variable dental phenotypes.
• Further investigation into EDAR variants can improve genetic counseling and understanding of TA etiology.