KDF1 is a novel candidate gene of non-syndromic tooth agenesis

Objective Tooth agenesis (TA) is featured by congenital loss of teeth, and can be divided into two subtypes, non-syndromic TA (NSTA) and syndromic TA (STA). Although 12 candidate genes of NSTA have been revealed, the genetic basis of NSTA needs to be further studied. We noticed an overlap of candidate genes between NSTA and STA, and hypothesized that some candidate genes of STA may be new candidate genes of NSTA. Methods Sanger sequencing, whole exome sequencing, bioinformatics analyses and immunohistochemical staining were performed to reveal the genetic basis of the patients in a family with NSTA. Results No pathogenic mutation was found in the 12 candidate genes of NSTA. We screened the variants of 76 STA candidate genes and identified a novel pathogenic mutation c.G908C (p.R303 P) in Keratinocyte Differentiation Factor 1 (KDF1). This mutation was cosegregated with the disease in the family. Bioinformatics analyses predicted the mutation to be pathogenic. Immunohistochemical staining of kdf1 in developing tooth germs indicated that kdf1 expression is important for the development of teeth. Conclusions This study identified KDF1 as a novel candidate gene for NSTA. STA candidate genes may be a promising source of new NSTA genes.