Mutations in the human homeobox MSX1 gene in the congenital lack of permanent teeth.

Tooth agenesis is the congenital lack of permanent teeth, which is called oligodontia, when the number of missing teeth is 6 or more. Oligodontia affects more than 1 of 100 humans, but its pathogenesis is largely unknown. Tooth genesis depends on the complex interactions between environmental and genetic factors. The MSX1 gene, a member of homeobox gene family, encodes a DNA-binding protein, which is involved in many epithelial-mesenchymal interactions, leading to vertebrate organogenesis, and appears to be most critical during early tooth development. The MSH1 gene has 2 exons, separated by an intron, and its mutations, such as missense or frame-shift mutations, have been reported to be associated with tooth agenesis. In the present study, we sequenced the MSX1 gene of three unrelated patients with sporadic, non-syndromic oligodontia: 2 boys aged 8.5 and 15 years old and one girl aged 15.5 years old. We have thus identified a homozygotic deletion of 11 nucleotides in the intron, near the 5' splicing site, in two patients, who also carry a different exonic transition. The base changes we detected were not present in an open reading-frame of the MSX1 gene, but the newly identified deletion of 11 nucleotides might interfere with the splicing of the MSX1 gene. In contrast, the third patient, a 15-year boy, displayed no base change in the examined regions. Therefore, the identified 11-nucleotide deletion may decrease the expression level of the MSX1 protein, but the link with oligodontia needs further study.