REFINED MAPPING OF A GENE FOR SPLIT HAND SPLIT FOOT MALFORMATION (SHFM3) ON CHROMOSOME 10Q25

Split hand-split foot malformation (SHFM) is a genetically heterogeneo us limb developmental defect characterised by the absence of digital r ays and syndactyly of the remaining digits. Three disease loci have re cently been mapped to chromosomes 7q21 (SHFM1), Xq26 (SHFM2), and 10q2 5 respectively (SHFM3). We report the mapping of SHFM3 to chromosome 1 0q25 in two large SHFM. families of French ancestry (Zmax for the comb ined families = 6.62 at theta = 0 for marker AFM239wc5 at locus D10S22 2). Two re-combinant events reduced the critical interval (D10S1709-co mbinant region to D10S1663) encompassing several candidate genes inclu ding a paired box gene PAX2 (Zmax = 5.35 at theta = 0). The fibroblast growth factor 8 (FGF 8), the retinol binding protein (RBP4), the zinc finger protein (ZNF32), and the homeobox genes HMX2 and HOX11 are als o good candidates by both their position and their function.