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.
