Comparative Analysis Of Rareedarmutations And Tooth Agenesis Pattern Inedar- Andeda-Associated Nonsyndromic Oligodontia

Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in theectodysplasin A receptor(EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigatedEDARmutations in multiplex nonsyndromic oligodontia and comparatively analyzed theEDAR- andEDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence ofEDARmutants.EDARmutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations ofEDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that theEDAR-related tooth agenesis pattern was markedly different fromEDA. The mandibular second premolars were most frequently missing (57.69%) inEDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern betweenEDAR- andEDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.