TY - JOUR
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 C.
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 C.
AU - Graff-Radford, Neill R.
AU - Boeve, Bradley F.
AU - Springer, Wolfdieter
AU - Wszolek, Zbigniew K.
AU - Dickson, Dennis W.
AU - Ross, Owen A.
N1 - Publisher Copyright:
© 2015 American Academy of Neurology.
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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U2 - 10.1212/WNL.0000000000002170
DO - 10.1212/WNL.0000000000002170
M3 - Article
C2 - 26561290
AN - SCOPUS:84949507560
SN - 0028-3878
VL - 85
SP - 2016
EP - 2025
JO - Neurology
JF - Neurology
IS - 23
ER -