Genetics of Huntington's disease and related disorders.
关键词
抽象
Huntington's disease is the most frequent form of the hereditary choreas and has a multifaceted phenotype including cognitive and psychiatric impairment. The disorder is due to a dynamic mutation, which also influences the onset age of the disorder. Other genetic modifiers of the HD phenotypes have been suggested but often not confirmed by independent studies. Several syndromes with similar presentation have different genetic backgrounds, including the neuroacanthocytoses, mainly choreoacanthocytosis and MacLeod syndrome as a result of mutations in chorein and Kell protein, respectively, but also benign hereditary chorea, owing to mutations in NKX-2-1, and paroxysmal kinesigenic dyskinesia, as a result of recently found mutations in the proline-rich transmembrane protein 2, PRRT2. Chorea can also be a major feature in other neurogenetic disorders, including the spinocerebellar ataxias and also in neurometabolic disorders.