ATP13A2 variability in Parkinson disease

Carles Vilariño-Güell, Alexandra I. Soto, Sarah J. Lincoln, Samia Ben Yahmed, Mounir Kefi, Michael G. Heckman, Mary M. Hulihan, Hua Chai, Nancy N. Diehl, Rim Amouri, Alex Rajput, Deborah C. Mash, Dennis W Dickson, Lefkos T. Middleton, Rachel A. Gibson, Faycal Hentati, Matthew J. Farrer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome (KRS), whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with nonfamilial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with nonfamilial PD and 38 healthy subjects from the United States. Sequencing analysis revealed 37 new variants; seven missense, six silent, and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with nonfamilial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or nonfamilial PD.

Original languageEnglish (US)
Pages (from-to)406-410
Number of pages5
JournalHuman Mutation
Volume30
Issue number3
DOIs
StatePublished - Mar 2009

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Parkinson Disease
Parkinsonian Disorders
Mutation
Exons
Brain
Tunisia
Messenger RNA
Pedigree
Introns
Healthy Volunteers
Gene Expression

Keywords

  • ATP13A2
  • Kufor-Rakeb syndrome
  • Parkinson
  • Parkinsonism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Vilariño-Güell, C., Soto, A. I., Lincoln, S. J., Yahmed, S. B., Kefi, M., Heckman, M. G., ... Farrer, M. J. (2009). ATP13A2 variability in Parkinson disease. Human Mutation, 30(3), 406-410. https://doi.org/10.1002/humu.20877

ATP13A2 variability in Parkinson disease. / Vilariño-Güell, Carles; Soto, Alexandra I.; Lincoln, Sarah J.; Yahmed, Samia Ben; Kefi, Mounir; Heckman, Michael G.; Hulihan, Mary M.; Chai, Hua; Diehl, Nancy N.; Amouri, Rim; Rajput, Alex; Mash, Deborah C.; Dickson, Dennis W; Middleton, Lefkos T.; Gibson, Rachel A.; Hentati, Faycal; Farrer, Matthew J.

In: Human Mutation, Vol. 30, No. 3, 03.2009, p. 406-410.

Research output: Contribution to journalArticle

Vilariño-Güell, C, Soto, AI, Lincoln, SJ, Yahmed, SB, Kefi, M, Heckman, MG, Hulihan, MM, Chai, H, Diehl, NN, Amouri, R, Rajput, A, Mash, DC, Dickson, DW, Middleton, LT, Gibson, RA, Hentati, F & Farrer, MJ 2009, 'ATP13A2 variability in Parkinson disease', Human Mutation, vol. 30, no. 3, pp. 406-410. https://doi.org/10.1002/humu.20877
Vilariño-Güell C, Soto AI, Lincoln SJ, Yahmed SB, Kefi M, Heckman MG et al. ATP13A2 variability in Parkinson disease. Human Mutation. 2009 Mar;30(3):406-410. https://doi.org/10.1002/humu.20877
Vilariño-Güell, Carles ; Soto, Alexandra I. ; Lincoln, Sarah J. ; Yahmed, Samia Ben ; Kefi, Mounir ; Heckman, Michael G. ; Hulihan, Mary M. ; Chai, Hua ; Diehl, Nancy N. ; Amouri, Rim ; Rajput, Alex ; Mash, Deborah C. ; Dickson, Dennis W ; Middleton, Lefkos T. ; Gibson, Rachel A. ; Hentati, Faycal ; Farrer, Matthew J. / ATP13A2 variability in Parkinson disease. In: Human Mutation. 2009 ; Vol. 30, No. 3. pp. 406-410.
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