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

Kotaro Ogaki, Shunsuke Koga, Michael G. Heckman, Fabienne 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 Carl Petersen, Neill R Graff Radford, Bradley F Boeve, Wolfdieter Springer, Zbigniew K Wszolek, Dennis W Dickson, Owen A Ross

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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
JournalNeurology
Volume85
Issue number23
DOIs
StatePublished - Dec 8 2015

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Lewy Bodies
Lewy Body Disease
Parkinson Disease
Genes
Exons
Gene Targeting
Parkinsonian Disorders
Fluorescent Antibody Technique
Immunohistochemistry
Population

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. / Ogaki, Kotaro; Koga, Shunsuke; Heckman, Michael G.; Fiesel, Fabienne; Ando, Maya; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Moussaud-Lamodière, Elisabeth L.; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Strongosky, Audrey J.; Uitti, Ryan J.; McCarthy, Allan; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Rudzinska, Monika; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Puschmann, Andreas; Nishioka, Kenya; Funayama, Manabu; Hattori, Nobutaka; Parisi, Joseph E; Petersen, Ronald Carl; Graff Radford, Neill R; Boeve, Bradley F; Springer, Wolfdieter; Wszolek, Zbigniew K; Dickson, Dennis W; Ross, Owen A.

In: Neurology, Vol. 85, No. 23, 08.12.2015, p. 2016-2025.

Research output: Contribution to journalArticle

Ogaki, K, Koga, S, Heckman, MG, Fiesel, F, Ando, M, Labbé, C, Lorenzo-Betancor, O, Moussaud-Lamodière, EL, Soto-Ortolaza, AI, Walton, RL, Strongosky, AJ, Uitti, RJ, McCarthy, A, Lynch, T, Siuda, J, Opala, G, Rudzinska, M, Krygowska-Wajs, A, Barcikowska, M, Czyzewski, K, Puschmann, A, Nishioka, K, Funayama, M, Hattori, N, Parisi, JE, Petersen, RC, Graff Radford, NR, Boeve, BF, Springer, W, Wszolek, ZK, Dickson, DW & Ross, OA 2015, 'Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders', Neurology, vol. 85, no. 23, pp. 2016-2025. https://doi.org/10.1212/WNL.0000000000002170
Ogaki, Kotaro ; Koga, Shunsuke ; Heckman, Michael G. ; Fiesel, Fabienne ; Ando, Maya ; Labbé, Catherine ; Lorenzo-Betancor, Oswaldo ; Moussaud-Lamodière, Elisabeth L. ; Soto-Ortolaza, Alexandra I. ; Walton, Ronald L. ; Strongosky, Audrey J. ; Uitti, Ryan J. ; McCarthy, Allan ; Lynch, Timothy ; Siuda, Joanna ; Opala, Grzegorz ; Rudzinska, Monika ; Krygowska-Wajs, Anna ; Barcikowska, Maria ; Czyzewski, Krzysztof ; Puschmann, Andreas ; Nishioka, Kenya ; Funayama, Manabu ; Hattori, Nobutaka ; Parisi, Joseph E ; Petersen, Ronald Carl ; Graff Radford, Neill R ; Boeve, Bradley F ; Springer, Wolfdieter ; Wszolek, Zbigniew K ; Dickson, Dennis W ; Ross, Owen A. / Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders. In: Neurology. 2015 ; Vol. 85, No. 23. pp. 2016-2025.
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abstract = "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.",
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T1 - Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders

AU - Ogaki, Kotaro

AU - Koga, Shunsuke

AU - Heckman, Michael G.

AU - Fiesel, Fabienne

AU - Ando, Maya

AU - Labbé, Catherine

AU - Lorenzo-Betancor, Oswaldo

AU - Moussaud-Lamodière, Elisabeth L.

AU - Soto-Ortolaza, Alexandra I.

AU - Walton, Ronald L.

AU - Strongosky, Audrey J.

AU - Uitti, Ryan J.

AU - McCarthy, Allan

AU - Lynch, Timothy

AU - Siuda, Joanna

AU - Opala, Grzegorz

AU - Rudzinska, Monika

AU - Krygowska-Wajs, Anna

AU - Barcikowska, Maria

AU - Czyzewski, Krzysztof

AU - Puschmann, Andreas

AU - Nishioka, Kenya

AU - Funayama, Manabu

AU - Hattori, Nobutaka

AU - Parisi, Joseph E

AU - Petersen, Ronald Carl

AU - Graff Radford, Neill R

AU - Boeve, Bradley F

AU - Springer, Wolfdieter

AU - Wszolek, Zbigniew K

AU - Dickson, Dennis W

AU - Ross, Owen A

PY - 2015/12/8

Y1 - 2015/12/8

N2 - 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.

AB - 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.

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