Update on Movement Disorders’ Genetics

Introduction:It is not hyperbolic if we claim that genetics has revolutionizedmovement disorders’ field in the recent decades. For example, the old view toParkinson disease as an absolutely nonhereditary disorder has changed to adisease with a multifactorial etiology in which genetic changes can be involvedat least in two ways: 1) monogenic causative mutations in rare cases and 2)low penetrant genetic variations in a large group of patients. Geneticresearches have significantly increased our knowledge about pathophysiologyof movement disorders. They have also contributed to earlier diagnosis ofsome disorders and they will potentially influence the future therapeutics.Area covered: In this review, clinical and neuropathologic findings of themain genetic etiologies for movement disorders are discussed.Opinion:Although some movement disorders such as Huntington disease arecaused by mutation or expanded repeats in a known gene, most otherdisorders are multifactorial and genetic variations play a significant role asprecipitating or predisposing factor in the pathogenesis of disease.Dominantly inherited (VPS35, SNCA, LRRK2) and recessively inherited(PARKIN, PINK1, DJ-1) Parkinson’s disease, isolated (TOR1A, GNAL, THAP1)and combined (GCH1, TH, ATP1A3, SGCE) dystonia, and paroxysmaldyskinesia (PRRT2, MR1, SLC2A1) are examples of movement disorders withmonogenic causes. On the other hand, GBA and MAPT variations which aredetected by novel genetic techniques such as genome-wide associationstudies and next-generation sequencing are samples of genetic variants thatare not directly etiologic for a familial type of movement disorders, but ratherrise susceptibility for and predisposition to a sporadic disease.

کلیدواژه ها:

Movement Disorders ، Genetic ، Parkinsonism ، Chorea ، Dystonia