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Although a few genetic factors have been reported to contribute to the disease, its mutational profiles have not been systemically studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To address the genetic profiles of clinically diagnosed MSA patients, exome sequencing and triplet repeat detection was conducted in 205 MSA patients, including one familial case. The pathogenicity of variants was determined according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the familial patient, a novel heterozygous <jats:italic>COQ2<\/jats:italic> pathogenic variant (p.Ala351Thr) was identified in the MSA pedigree. In the sporadic patients, 29 pathogenic variants were revealed in 21 genes, and the <jats:italic>PARK7<\/jats:italic> p.Ala104Thr variant was significantly associated with MSA (<jats:italic>p<\/jats:italic>\u2009=\u20090.0018). Moreover, burden tests demonstrated that the pathogenic variants were enriched in cerebellar ataxia\u2010related genes in patients. Furthermore, repeat expansion analyses revealed that two patients carried the pathogenic CAG repeat expansion in the CACNA1A gene (SCA6), one patient carried the (ACAGG)exp\/(ACAGG)exp expansion in <jats:italic>RFC1<\/jats:italic> and one carried the GAA\u2010pure expansion in <jats:italic>FGF14<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In conclusion, a novel <jats:italic>COQ2<\/jats:italic> pathogenic variant was identified in a familial MSA patient, and repeat expansions in CACNA1A, RFC1 and FGF14 gene were detected in four sporadic patients. Moreover, a <jats:italic>PARK7 variant<\/jats:italic> and the burden of pathogenic variants in cerebellar ataxia\u2010related genes were associated with MSA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16441","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T06:44:45Z","timestamp":1723877085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic profiles of multiple system atrophy revealed by exome sequencing, long\u2010read sequencing and spinocerebellar ataxia repeat expansion analysis"],"prefix":"10.1111","volume":"31","author":[{"given":"Xu\u2010Ying","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology Xuanwu Hospital of Capital Medical University, National Clinical Research Centre for Geriatric Diseases  Beijing 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