Dominant spinocerebellar ataxias: a molecular approach to classification, diagnosis, pathogenesis and the future.
The capacity to use molecular techniques to establish the genetic diagnoses of the autosomal dominant ataxias has revolutionized the field. It is now possible to systematically classify these disorders according to the nature of the causative mutation, with implications for diagnostic testing, analysis of pathogenesis and therapeutic strategies. Here, the disorders are grouped into ataxias caused by CAG repeat expansions that encode polyglutamine, ataxias caused by mutations in ion channels, ataxias caused by repeat expansions that do not encode polyglutamine, and ataxias caused by point mutations. The clinical, pathological, genetic and pathogenic features of each disorder are considered and the current status and future of diagnosis and therapy are reviewed in light of this classification scheme.
Margolis
Russell L
RL
Department of Psychiatry, Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. rmargoli@jhmi.edu
D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D025202:Molecular Diagnostic Techniques; D010455:Peptides / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D018911:Trinucleotide Repeats
D007473:Ion Channels; D010455:Peptides; C097188:polyglutamine