Refined mapping of the gene for otopalatodigital syndrome type I.

Otopalatodigital syndrome type I (OPD-I) (MIM 31130) is a rare X linked disorder characterised by a peculiar face with supraorbital ridges, flat nasal bridge, hypertelorism, micrognathia, and cleft palate (pugilistic face) and by hand and foot deformities with spatulate distal digits and short first digits arising from the second digits (tree frog hands and feet), together with conductive deafness, short stature, and mild mental retardation. 2 Affected males invariably have a distinct phenotype, and heterozygous carrier females frequently exhibit a mild phenotype with an estimated penetrance of ∼80%. The gene for OPD-I has been mapped to the Xq27-28 region by linkage analyses in two families. Hoar et al localised the OPD-I gene to a region distal to DXS100 on Xq25, with a maximum lod score of 1.20 at θ=0 for DXS86 on Xq26 and for DXS304 and DXS15 on Xq28. Biancalana et al assigned the OPD-I gene to a region distal to DXS539 on Xq27, with a maximum lod score of 1.99 at θ=0 for DXS305 and DXS52 on Xq28, and excluded linkage to DXS86 on Xq26. These findings suggest that the gene for OPD-I resides in the approximately 12 Mb region distal to DXS539 on Xq27, with a combined lod score of 3.19. Here, we report a Japanese family with OPD-I and refine the OPD-I critical region.