Multiple system atrophy: the application of genetics in understanding etiology

摘要: Classically defined phenotypically by a triad of cerebellar ataxia, parkinsonism, and autonomic dysfunction in conjunction with pyramidal signs, multiple system atrophy (MSA) is rare progressive neurodegenerative disease affecting an estimated 3–4 per every 100,000 individuals among adults 50–99 years age. With pathological hallmark alpha-synuclein-immunoreactive glial cytoplasmic inclusions (GCIs; Papp–Lantos inclusions), MSA patients exhibit marked changes the striatonigral and/or olivopontocerebellar structures brain. As member alpha-synucleinopathy family, which its well-demarcated aggregation, MSA’s clinical presentation exhibits several overlapping features other members including Parkinson’s (PD) dementia Lewy bodies (DLB). Given extensive fund knowledge regarding genetic etiology PD revealed within past years, investigation warranted. While current genome-wide association study underway for to further clarify role associated loci single-nucleotide polymorphisms, cases have presented solid preliminary evidence etiology. Naturally, genes variants manifesting known associations (and similar disorders), SNCA MAPT, been comprehensively investigated patient cohorts. More recently COQ2 linked Japanese population although this finding awaits replication. Nonetheless, significant positive subsequent independent replication studies scarce. very limited information mutations or alterations gene dosage as cause MSA, search novel risk genes, may be form common variants, logical nexus research. We believe that application next generation methods will provide valuable insight into underlying causes disease, central identification etiologic-based therapies.