A novel frameshift MSX1 mutation in a Saudi family with autosomal dominant premolar and third molar agenesis

•Consanguineous Saudi family with autosomal dominant non-syndromic tooth agenesis.•Exome sequencing technique was used to search the genome for genetic variants.•MSX1 mutation (c.750_751insACCGGCTGCC, p.F251PfsX92) was found in exon 2.

ObjectivesIn this study, the aim was to investigate a consanguineous Saudi family with non-syndromic premolars and third molars agenesis and to identify the causal mutation(s) using whole exome sequencing.DesignFamily phenotype and family pedigree were constructed from clinical and radiographic examinations. Whole exome sequencing was performed in two affected members of the Saudi family using the SureSelect Human all Exon 50 Mb kit (Agilent Technologies, Inc., Santa Clara, CA) and then sequenced on an Illumina HiSeq. SNP and indel calling were performed using samtools version 0.18 and were annotated using the software ANNOVAR.ResultsThe family pedigree showed that the inheritance was autosomal dominant. Whole exome sequencing revealed that the affected members in this family were heterozygous with a novel frameshift mutation in exon 2 of the MSX1 gene, (NM_002448:c.750_751insACCGGCTGCC, p.F251PfsX92).ConclusionsThe novel MSX1 frameshift mutation was linked to a family with moderate to severe tooth agenesis phenotype affecting second premolars and third molars in both arches. This expands the genotype–phenotype of MSX1 associated conditions.