A MUSCLE-SPECIFIC DNASE I-LIKE GENE IN HUMAN XQ28

A novel cDNA which maps to human Xq28 has been isolated and characterized. Sequence similarity to DNase I is high at the DNA and peptide sequence levels. The transcript is present at highest levels in skeletal and cardiac muscle, with lower expression in other tissues. Mutation analysis has been performed using DNA samples from two unrelated patients with Earth syndrome, and from 11 unrelated patients with Emery-Dreifuss muscular dystrophy, two genetic disorders linked to Xq28. No disease-associated mutations were detected in the coding region of the gene; however, a novel 190 base pair insertion/ deletion polymorphism was found in the 3' untranslated region. Translation of the long open reading frame found in the cDNA yields a putative 302 amino acid protein with 37.6% identity to human DNase I. The protein is predicted to contain a signal sequence at the amino terminus, a transmembrane domain near the carboxyl terminus, and a helix-loop-helix domain.