Clinical Autonomic Research

, Volume 24, Issue 1, pp 25–30

SHC2 gene copy number in multiple system atrophy (MSA)

  • Marcus C. Ferguson
  • Emily M. Garland
  • Lora Hedges
  • Bethany Womack-Nunley
  • Rizwan Hamid
  • John A. PhillipsIII
  • Cyndya A. Shibao
  • Satish R. Raj
  • Italo Biaggioni
  • David Robertson
Research Article

DOI: 10.1007/s10286-013-0216-8

Cite this article as:
Ferguson, M.C., Garland, E.M., Hedges, L. et al. Clin Auton Res (2014) 24: 25. doi:10.1007/s10286-013-0216-8

Abstract

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.

Keywords

Multiple system atrophy Genetics Copy number variation Movement disorders, SHC2 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Marcus C. Ferguson
    • 1
  • Emily M. Garland
    • 1
  • Lora Hedges
    • 4
    • 5
  • Bethany Womack-Nunley
    • 4
    • 5
  • Rizwan Hamid
    • 4
    • 5
  • John A. PhillipsIII
    • 4
    • 5
  • Cyndya A. Shibao
    • 1
  • Satish R. Raj
    • 1
  • Italo Biaggioni
    • 1
    • 2
  • David Robertson
    • 1
    • 2
    • 3
  1. 1.Autonomic Dysfunction Center, Department of MedicineVanderbilt UniversityNashvilleUSA
  2. 2.Department of PharmacologyVanderbilt UniversityNashvilleUSA
  3. 3.Department of NeurologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of PediatricsVanderbilt UniversityNashvilleUSA
  5. 5.Department of GeneticsVanderbilt UniversityNashvilleUSA