PURPOSE: Multiple system atrophy (MSA) is a sporadic, late onset, rapidly progressing neurodegenerative disorder, which is characterized by autonomic failure, together with Parkinsonian, cerebellar, and pyramidal motor symptoms. The pathologic hallmark is the glial cytoplasmic inclusion with α-synuclein aggregates. MSA is thus an α-synucleinopathy. Recently, Sasaki et al. reported that heterozygosity for copy number loss of Src homology 2 domain containing-transforming protein 2 (SHC2) genes (heterozygous SHC2 gene deletions) occurred in DNAs from many Japanese individuals with MSA. Because background copy number variation can be distinct in different human populations, we assessed SHC2 allele copy number in DNAs from a US cohort of individuals with MSA, to determine the contribution of SHC2 gene copy number variation in an American cohort followed at a US referral center for MSA. Our cohort included 105 carefully phenotyped individuals with MSA. METHODS: We studied 105 well-characterized patients with MSA and 5 control subjects with reduced SHC2 gene copy number. We used two TaqMan Gene Copy Number Assays, to determine the copy number of two segments of the SHC2 gene that are separated by 27 kb. RESULTS: Assay results of DNAs from all of our 105 subjects with MSA showed 2 copies of both segments of their SHC2 genes. CONCLUSION: Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds.
PURPOSE:Multiple system atrophy (MSA) is a sporadic, late onset, rapidly progressing neurodegenerative disorder, which is characterized by autonomic failure, together with Parkinsonian, cerebellar, and pyramidal motor symptoms. The pathologic hallmark is the glial cytoplasmic inclusion with α-synuclein aggregates. MSA is thus an α-synucleinopathy. Recently, Sasaki et al. reported that heterozygosity for copy number loss of Src homology 2 domain containing-transforming protein 2 (SHC2) genes (heterozygous SHC2 gene deletions) occurred in DNAs from many Japanese individuals with MSA. Because background copy number variation can be distinct in different human populations, we assessed SHC2 allele copy number in DNAs from a US cohort of individuals with MSA, to determine the contribution of SHC2 gene copy number variation in an American cohort followed at a US referral center for MSA. Our cohort included 105 carefully phenotyped individuals with MSA. METHODS: We studied 105 well-characterized patients with MSA and 5 control subjects with reduced SHC2 gene copy number. We used two TaqMan Gene Copy Number Assays, to determine the copy number of two segments of the SHC2 gene that are separated by 27 kb. RESULTS: Assay results of DNAs from all of our 105 subjects with MSA showed 2 copies of both segments of their SHC2 genes. CONCLUSION: Our results indicate that SHC2 gene deletions underlie few, if any, cases of well-characterized MSA in the US population. This is in contrast to the Japanese experience reported by Sasaki et al., likely reflecting heterogeneity of the disease in different genetic backgrounds.
Authors: Erin L Heinzen; Rodney A Radtke; Thomas J Urban; Gianpiero L Cavalleri; Chantal Depondt; Anna C Need; Nicole M Walley; Paola Nicoletti; Dongliang Ge; Claudia B Catarino; John S Duncan; Dalia Kasperaviciūte; Sarah K Tate; Luis O Caboclo; Josemir W Sander; Lisa Clayton; Kristen N Linney; Kevin V Shianna; Curtis E Gumbs; Jason Smith; Kenneth D Cronin; Jessica M Maia; Colin P Doherty; Massimo Pandolfo; David Leppert; Lefkos T Middleton; Rachel A Gibson; Michael R Johnson; Paul M Matthews; David Hosford; Reetta Kälviäinen; Kai Eriksson; Anne-Mari Kantanen; Thomas Dorn; Jörg Hansen; Günter Krämer; Bernhard J Steinhoff; Heinz-Gregor Wieser; Dominik Zumsteg; Marcos Ortega; Nicholas W Wood; Julie Huxley-Jones; Mohamad Mikati; William B Gallentine; Aatif M Husain; Patrick G Buckley; Ray L Stallings; Mihai V Podgoreanu; Norman Delanty; Sanjay M Sisodiya; David B Goldstein Journal: Am J Hum Genet Date: 2010-04-15 Impact factor: 11.025
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Authors: Alessandra Fanciulli; Fabian Leys; Fabienne Lehner; Victoria Sidoroff; Viktoria C Ruf; Cecilia Raccagni; Philipp Mahlknecht; Demy J S Kuipers; Wilfred F J van IJcken; Heike Stockner; Thomas Musacchio; Jens Volkmann; Camelia Maria Monoranu; Iva Stankovic; Guido Breedveld; Federico Ferraro; Christina Fevga; Otto Windl; Jochen Herms; Stefan Kiechl; Werner Poewe; Klaus Seppi; Nadia Stefanova; Sonja W Scholz; Vincenzo Bonifati; Gregor K Wenning Journal: Brain Commun Date: 2022-07-04
Authors: Kotaro Ogaki; Shinsuke Fujioka; Michael G Heckman; Sruti Rayaprolu; Alexandra I Soto-Ortolaza; Catherine Labbé; Ronald L Walton; Oswaldo Lorenzo-Betancor; Xue Wang; Yan Asmann; Rosa Rademakers; Neill Graff-Radford; Ryan Uitti; William P Cheshire; Zbigniew K Wszolek; Dennis W Dickson; Owen A Ross Journal: Mol Neurodegener Date: 2014-11-05 Impact factor: 14.195