Clinical and genetic studies on 12 preaxial polydactyly families and refinement of the localisation of the gene responsible to a 1.9 cM region on chromosome 7q36

Polydactyly is the most frequently observed congenital hand malformation wi th a prevalence between 5 and 19 per 10000 live births. It can occur as an isolated disorder, in association with other hand/foot malformations, or as a part of a syndrome, and is usually inherited as an autosomal dominant tr ait. According to its anatomical location, polydactyly can be generally sub divided into pre- and postaxial forms. Recently, a gene responsible for pre axial polydactyly types II and III, as well as complex polysyndactyly, has been localised to chromosome 7q36. In order to facilitate the search for the underlying genetic defect, we asc ertained 12 additional families of different ethnic origin affected with pr eaxial polydactyly. Eleven of the kindreds investigated could be linked to chromosome 7q36, enabling us to refute the critical region for the preaxial polydactyly gene to a region of 1.9 cM. Our findings also indicate that ra dial and tibial dysplasia/aplasia can be associated with preaxial polydacty ly on chromosome 7q36. Combining our results with other studies suggests that all non-syndromic pr eaxial polydactylies associated with triphalangism of the thumb are caused by a single genetic locus, but that there is genetic heterogeneity for prea xial polydactyly associated with duplications of biphalangeal thumbs. Compa rison of the phenotypic and genetic findings of different forms of preaxial polydactyly is an important step in analysing and understanding the aetiol ogy and pathogenesis of these limb malformations.