title: SHC2 gene copy number in multiple system atrophy (MSA).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Autonomic Dysfunction Center, Department of Medicine, Vanderbilt University, AA3228 Medical Center North, Nashville, TN, 37232-2195, USA, marcus.ferguson@vanderbilt.edu.
authors.forename: Marcus C
authors.initials: MC
authors.lastname: Ferguson
authors.forename: Emily M
authors.initials: EM
authors.lastname: Garland
authors.forename: Lora
authors.initials: L
authors.lastname: Hedges
authors.forename: Bethany
authors.initials: B
authors.lastname: Womack-Nunley
authors.forename: Rizwan
authors.initials: R
authors.lastname: Hamid
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.forename: David
authors.initials: D
authors.lastname: Robertson
mesh_terms: D000368:Aged; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics*; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2; D014481:United States / Q000453:epidemiology
chemical_list: C099021:SHC2 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071426:Src Homology 2 Domain-Containing, Transforming Protein 2