Novel MSX1 mutation in a family with autosomal-dominant hypodontia of second premolars and third molars

Objective: Tooth agenesis is the most common developmental anomaly of the human dentition, with aetiology involving both genetic and environmental factors. The aim of the study was to search for casual mutations underlying hypodontia in a family with agenesis of the second premolars and third molars.

Design: Direct sequencing of the coding regions including exon-intron boundaries of the MSX1 and PAX9 genes was performed in all affected family members.

Results: Novel heterozygous mutation segregating in an autosomal dominant model was identified in the MSX1 gene. This c.T671C transition leads to a substitution of leucine by proline at position 224, which is the penultimate amino acid residue of the highly conserved homeodomain. None of the control subjects (600 chromosomes) were carriers of this novel, probably damaging to protein function, mutation.

Conclusions: Our results demonstrate for the first time that MSX1 might play a substantial role in familial cases of hypodontia involving only second premolars and third molars. The novel c.T671C mutation might be the etiological variant of the MSX1 gene responsible for the lack of permanent teeth in the tested family.