Non-syndromic severe hypodontia caused by a novel frameshift insertion mutation in the homeobox of the MSX1 gene

•A novel mutation in the human MSX1 gene linked to non-syndomic hypodontia.•Identification of mutation in two siblings using exome sequencing.•Frameshift mutation in homeobox region of MSX1.

ObjectiveInherited congenital anomalies in tooth number, particularly hypodontia are relatively common. Although substantial progress has been made that permits a better understanding of the causes of tooth agenesis, overall knowledge of the phenotype:genotype correlations in this anomaly are still lacking. The aim in this study was to identify the causal gene mutation(s) in a family of two sisters with severe hypodontia (oligodontia) including 2nd premolars and 1st and 3rd molars, using whole exome sequencing (WES).MethodsWES was performed using in-solution hybridization, followed by massively parallel sequencing.ResultsA frameshift insertion of 7 basepairs (GCAAGTT) in the homebox of MSX1 gene located in the exon 2 in heterozygous state has been identified in both sisters (NM_002448:exon2:c.572_573ins GCAAGTT: p.F191fs).ConclusionWe conclude that this frameshift mutation in the homeodomain (which plays an essential role in DNA binding) of MSX1 gene is responsible for tooth agenesis in this family. This expands the phenotype-genotype correlation associated with MSX1 mutations.