ANALYSIS OF THE HUMAN SONIC-HEDGEHOG CODING AND PROMOTER REGIONS IN SACRAL AGENESIS, TRIPHALANGEAL THUMB, AND MIRROR POLYDACTYLY

The human Sonic Hedgehog gene (SHH) is one of the vertebrate homologs related to the Drosophila segment polarity gene hedgehog. The entire c oding and promoter region of the SHH gene, including 2 kb 5' of the tr anscriptional start site has been screened for mutations in families w ith autosomal dominant sacral agenesis and autosomal dominant triphala ngeal thumb, two conditions previously known to be Linked to 7q36. We have also studied the SHH gene in five families with minor polydactyly associated with tibial hemimelia and in 51 unrelated patients with ne ural tube defects. Except for two sequence variants in exon 3, no muta tions were found in these disease categories.