Next-generation sequencing applied to non-syndromic tooth agenesis: A systematic literature review

To explore the genetic profile of Non-Syndromic Tooth Agenesis (NSTA) detected by Next-Generation Sequencing (NGS). A systematic review exploring PubMed, ScienceDirect, BMC, LILACS, Scopus, Embase and Web of Science was conducted. Studies investigating the genetic alterations involved in NSTA detected by NGS were selected. Data were extracted and risks of biases were evaluated. After screening 191 articles, 4 articles were included in this study. The overall qualities of the studies were considered high for 3 papers and low for the other one. Among 636 permanent missing teeth, second premolars and lateral incisors were the most affected ones. Whole exome sequencing and gene panel sequencing focusing either on exons plus exon-intron boundaries, or only exons were focused. Mutations on MSX1, PAX9, EDA, EDAR, AXIN2, WNT10A, LAMA3, DKK1, COL17A1, IRF6, LRP6, CHD7, CREBBP, EVC, LEF1, ROR2, TBX22, FGFR1 and TP63 were identified. Allelic frequencies of some variants were reported only in polish and Turkish populations and showing both slight and important variations. Moreover, Functional analysis was performed only for LRP6 variant in Turkish population. The published in-silico analyses of the proteins corresponding to the mutated LAMA3, MSX1 and WNT10 genes revealed a truncated protein for MSX1 and disulfide bridges destabilization for LAMA3 and WNT10A. Several genes were associated with NSTA and the candidacy of novel genes was suggested. Further research focusing on the exon-intron boundaries and the impact of mutations on the antisense transcripts should be carried out to better puzzle out their impact on the protein translation and structure. •Gene panel & whole exome sequencing were used to explore genetics of tooth agenesis.•Targeting the exon-intron boundaries helps understanding the pre-mRNA splicing.•Our study revealed novel risk genes associated with non-syndromic tooth agenesis.•Differences in allelic frequencies were reported between the studied populations.•Variants in the involved genes affect the protein structure & RNA splicing process.