Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders

Kotaro Ogaki, Shunsuke Koga, Michael G. Heckman, Fabienne C. Fiesel, Maya Ando, Catherine Labbé, Oswaldo Lorenzo-Betancor, Elisabeth L. Moussaud-Lamodière, Alexandra I. Soto-Ortolaza, Ronald L. Walton, Audrey J. Strongosky, Ryan J. Uitti, Allan McCarthy, Timothy Lynch, Joanna Siuda, Grzegorz Opala, Monika Rudzinska, Anna Krygowska-Wajs, Maria Barcikowska, Krzysztof CzyzewskiAndreas Puschmann, Kenya Nishioka, Manabu Funayama, Nobutaka Hattori, Joseph E. Parisi, Ronald C. Petersen, Neill R. Graff-Radford, Bradley F. Boeve, Wolfdieter Springer, Zbigniew K. Wszolek, Dennis W. Dickson, Owen A. Ross

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations. Methods: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls). Immunohistochemistry and immunofluorescence studies were performed on pathologic LBD cases with rare CHCHD2 variants. Results: We identified 9 rare exonic variants of unknown significance. These variants were more frequent in the combined group of PD and LBD patients compared to controls (0.6% vs 0.1%, p = 0.013). In addition, the presence of any rare variant was more common in patients with LBD (2.5% vs 1.0%, p = 0.050) compared to controls. Eight of these 9 variants were located within the gene's mitochondrial targeting sequence. Conclusions: Although the role of variants of the CHCHD2 gene in PD and LBD remains to be further elucidated, the rare variants in the mitochondrial targeting sequence may be a risk factor for Lewy body disorders, which may link CHCHD2 to other genetic forms of parkinsonism with mitochondrial dysfunction.

Original languageEnglish (US)
Pages (from-to)2016-2025
Number of pages10
Issue number23
StatePublished - Dec 8 2015

ASJC Scopus subject areas

  • Clinical Neurology


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