Mutation Identification And Functional Analysis Of ADAR, The Disease Gene For Dyschromatosis Symmetrica Hereditaria

Dyschromatosis symmetrica hereditaria (DSH, MIM# 127400) is an autosomal dominant skin disorder, characterized by the presence of hyperpigmented and hypopigmented macules mostly on the dorsal aspects of the extremities. The onset of the disease is usually during infancy or childhood, and 73% of patients develop the skin lesions before 6 years of age. The DSH locus has recently been mapped to chromosome Iq11-q21 and pathogenic mutations were identified in ADAR, the gene encoding double-stranded RNA-specific adenosine deaminase, in Japanese patients with DSH.ADAR (adenosine deaminases acting on RNA) is involved in site-selective RNA editing that changes adenosine residues to inosine in double-stranded RNA (dsRNA) and messenger RNA (mRNA). It affects multiple biological processes in various species from Homo sapiens to Caenorhabditis elegans. Human ADAR spans 30 kb and contains 15 exons. Two isoforms of the ADAR protein are known, whose translations initiate from Met 1 (Ml) and Met 296 (M296), respectively. Ml, the longest protein encoded, is a 1,226-amino-acid one possessing, from N- to C- terminals, one nuclear export signal...