A SPLIT HAND-SPLIT FOOT (SHFM3) GENE IS LOCATED AT 10Q24-]25

The split hand-split foot (SHSF) malformation affects the central rays of the upper and lower limbs. It presents either as an isolated defec t or in association with other skeletal or non-skeletal abnormalities. An autosomal SHSF locus (SHFM1) was previously mapped to 7q22.1. We r eport the mapping of a second autosomal SHSF locus to 10q24->25. A pan el of families was tested with 17 marker loci mapped to the 10q24->25 region. Maximum lod scores of 3.73, 4.33 and 4.33 at a recombination f raction of zero were obtained for the loci D10S198, PAX2 and D10S1239, respectively. An 19 cM critical region could be defined by haplotype analysis and several genes with a potential role in limb morphogenesis are located in this region. Heterogeneity testing indicates the exist ence of at least one additional autosomal SHSF locus.