Novel MSX1 frameshift causes autosomal-dominant oligodontia

Can kindreds with tooth agenesis caused by MSX1 or PAX9 mutations be distinguished by their phenotypes? We have identified an MSX1 frameshift mutation (g.62dupG, p.G22RfsXI68) that causes non-syndromic autosomal-dominant oligodontia, featuring the absence of multiple permanent teeth, including all second bicuspids and mandibular central incisors. The dominant phenotype is apparently due to haploinsufficiency. We analyzed patterns of partial tooth agenesis in seven kindreds with defined MSX1 mutations and ten kindreds with defined PAX9 mutations. The probability of missing a particular type of tooth is always bilaterally symmetrical, but differences exist between the maxilla and mandible. MSX1-associated oligodontia typically includes missing maxillary and mandibular second bicuspids and maxillary first bicuspids. The most distinguishing feature of MSX1-associated oligodontia is the frequent (75%) absence of maxillary first bicuspids, while the most distinguishing feature of PAX9-associated oligodontia is the frequent (> 80%) absence of the maxillary and mandibular second molars.