A 2ND AUTOSOMAL SPLIT HAND SPLIT FOOT LOCUS MAPS TO CHROMOSOME 10Q24-Q25

Ectrodactyly (split hand/split foot malformation, SHSF) is a human lim b malformation characterized by absent central digital rays, deep medi an cleft, and syndactyly of remaining digits. The disorder is genetica lly heterogeneous, with at least two loci thus far determined: an auto somal locus at 7q21 designated SHFM1 and an X-linked locus at Xq26 des ignated SHFM2. Cytogenetic analysis of sporadic SHSF patients and link age studies in extended pedigrees both suggest more than one autosomal locus exists. We report a novel SHSF locus suggested by a stillborn i nfant with ectrodactyly and other malformations who inherited an unbal anced translocation resulting in monosomy 4p15.1-4pter and trisomy for 10q25.2-qter. To investigate 10q25 as a possible split hand/ split fo ot locus, microsatellite markers spanning 52 cM of 10q were utilized f or linkage analysis of a large autosomal dominant SHSF pedigree in whi ch the region encompassing SHFM1 previously was excluded as containing the causative mutation. The marker D10S583 was fully informative in t he family, giving a maximum LOD score of 4.21 at recombination theta = 0.00. Recombination haplotypes define the 9 cM region between D10S541 and D10S574 as inclusive for this second autosomal SHSF locus, for wh ich we propose the designation SHFM3.