Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing

Tooth agenesis is described as the absence of one or more teeth. It is caused by a failure in tooth development and is one of the most common human developmental anomalies. We herein report genomic analyses of selective mandibular incisor agenesis (SMIA) using exome sequencing. Two Japanese families with SMIA were subjected to exome sequencing, and family with sequence similarity 65 member A (FAM65), nuclear factor of activated T-cells 3 (NFATC3) and cadherin-related 23 gene (CDH23) were detected. In the follow-up study, 51 Japanese and 32 Korean sporadic patients with SMIA were subjected to exome analyses, and 18 reported variants in PAX9, AXIN2, EDA, EDAR, WNT10A, BMP2 and GREM2 and 27 variants of FAM65, NFATC3 and CDH23 were found in 38 patients. Our comprehensive genetic study of SMIA will pave the way for a full understanding of the genetic etiology of SMIA and provide targets for treatment.