Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.

Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval.