Identification of a Novel Mutation in LRP6 Gene Responsible for Non-Syndromic Hypodontia in a Palestinian Family

Abstract

Background: Hypodontia is considered one of the most common developmental anomalies in humans. It is defined as the missing of one or more primary or secondary teeth which results in disturbances during the early stages of tooth development. These disturbances are mostly due to genetic causes either syndromic or non-syndromic. Mainly, mutations in three genes have been identified in human: MSX1, PAX9 and AXIN2 through studying familial hypodontia pedigrees. Worldwide, permanent teeth missing prevalence ranges between 2.6%–11.3% of the population (missing primary teeth show very low prevalence). The aim of our study was to identify the genetic determinants of non-syndromic hypodontia in a Palestinian family. Methods: Eight blood samples were collected from members of the study family and DNA was extracted. Whole exome sequencing then Sanger sequencing were used to investigate the causative mutation. The mutation detected in the study was screened by Sanger Sequencing in 200 normal controls. Results: Whole exome sequencing revealed a novel heterozygous mutation (C>G) in Lowdensity lipoprotein receptor-related protein 6 (LRP6) gene which results in R675G alteration and hence alter the protein structure. The 200 controls were negative for the LRP6 variant. Conclusion: Our results revealed a novel mutation in LRP6 gene that disrupts tooth development and results in non-syndromic hypodontia in human. Keywords: hypodontia, LRP6, Wnt signaling pathway.