Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy
| العنوان: | Mutations in COQ2 in Familial and Sporadic Multiple-System Atrophy |
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| المؤلفون: | Masahiro Horiuchi, Osamu Onodera, Takamichi Hattori, Jun Mitsui, Jun Goto, Kenju Hara, Katsuhiko Shirahige, Sid Gilman, Laurie J. Ozelius, Hidehiro Mizusawa, Hidenao Sasaki, Hiroyuki Soma, Kazuaki Kanai, Ullrich Wallner, Alessandro Filla, Tatsushi Toda, Yoshiyuki Kuroiwa, Akiyoshi Kakita, Thomas Klockgether, Alexandra Durr, Yuishin Izumi, Yoshio Momose, Kinya Ishikawa, Susumu Kusunoki, Virginia M.-Y. Lee, Wataru Satake, Hidetoshi Date, Garth A. Nicholson, Budrul Ahsan, Makiko Komata, Alexis Brice, Yaeko Ichikawa, Atsushi Iwata, Kenichi Yasui, Caroline M. Tanner, Yorihiro Yamamoto, Satoshi Kuwabara, Masashi Aoki, Yuji Takahashi, Takeo Kato, Gen Sobue, Yasushi Osaki, Mitsutoshi Yamamoto, Ichiro Yabe, Hirohisa Watanabe, Paola Sandroni, Ryozo Kuwano, Hitoshi Takahashi, Eliezer Masliah, Hiroyuki Ishiura, Mizuki Ito, Tatsuhiko Yuasa, Tatiana Foroud, Shoji Tsuji, Kazuko Hasegawa, Kimihito Arai, Mitsunori Yamada, Takashi Matsukawa, Shigeo Murayama, John Q. Trojanowski, Shigeru Koyano, Tomoyoshi Kondo, Masatoyo Nishizawa, Yoko Fukuda, Kenji Nakashima, Nobutaka Hattori, Hiroshi Takashima, Miho Murata, Phillip A. Low, Clifford W. Shults, Walter A. Kukull, Hijiri Ito, Yasuo Nakahara, Ryuji Kaji |
| المساهمون: | Mitsui, J, Matsukawa, T, Ishiura, H, Fukuda, Y, Ichikawa, Y, Date, H, Ahsan, B, Nakahara, Y, Momose, Y, Takahashi, Y, Iwata, A, Goto, J, Yamamoto, Y, Komata, M, Shirahige, K, Hara, K, Kakita, A, Yamada, M, Takahashi, H, Onodera, O, Nishizawa, M, Takashima, H, Kuwano, R, Watanabe, H, Ito, M, Sobue, G, Soma, H, Yabe, I, Sasaki, H, Aoki, M, Ishikawa, K, Mizusawa, H, Kanai, K, Hattori, T, Kuwabara, S, Arai, K, Koyano, S, Kuroiwa, Y, Hasegawa, K, Yuasa, T, Yasui, K, Nakashima, K, Ito, H, Izumi, Y, Kaji, R, Kato, T, Kusunoki, S, Osaki, Y, Horiuchi, M, Kondo, T, Murayama, S, Hattori, N, Yamamoto, M, Murata, M, Satake, W, Toda, T, Dürr, A, Brice, A, Filla, Alessandro, Klockgether, T, Wüllner, U, Nicholson, G, Gilman, S, Shults, Cw, Tanner, Cm, Kukull, Wa, Lee, Vm, Masliah, E, Low, Pa, Sandroni, P, Trojanowski, Jq, Ozelius, L, Foroud, T, Tsuji, S. |
| المصدر: | The New England journal of medicine 369(3), 233-244 (2013). doi:10.1056/NEJMoa1212115 |
| بيانات النشر: | Massachusetts Medical Society, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Genetic Linkage, Ubiquinone, DNA Mutational Analysis, Cell Line, World Wide Web, Atrophy, coenzyme Q10, Humans, Medicine, 4-hydroxybenzoate polyprenyltransferase, ddc:610, analysis [Ubiquinone], analogs & derivatives [Ubiquinone], Brain Chemistry, Thesaurus (information retrieval), Alkyl and Aryl Transferases, business.industry, General Medicine, genetics [Alkyl and Aryl Transferases], medicine.disease, Pedigree, Mutation, Female, genetics [Multiple System Atrophy], business |
| الوصف: | Multiple-system atrophy is an intractable neurodegenerative disease characterized by autonomic failure in addition to various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. Although multiple-system atrophy is widely considered to be a nongenetic disorder, we previously identified multiplex families with this disease, which indicates the involvement of genetic components.In combination with linkage analysis, we performed whole-genome sequencing of a sample obtained from a member of a multiplex family in whom multiple-system atrophy had been diagnosed on autopsy. We also performed mutational analysis of samples from members of five other multiplex families and from a Japanese series (363 patients and two sets of controls, one of 520 persons and one of 2383 persons), a European series (223 patients and 315 controls), and a North American series (172 patients and 294 controls). On the basis of these analyses, we used a yeast complementation assay and measured enzyme activity of parahydroxybenzoate-polyprenyl transferase. This enzyme is encoded by the gene COQ2 and is essential for the biosynthesis of coenzyme Q10. Levels of coenzyme Q10 in lymphoblastoid cells and brain tissue were measured on high-performance liquid chromatography.We identified a homozygous mutation (M78V-V343A/M78V-V343A) and compound heterozygous mutations (R337X/V343A) in COQ2 in two multiplex families. Furthermore, we found that a common variant (V343A) and multiple rare variants in COQ2, all of which are functionally impaired, are associated with sporadic multiple-system atrophy. The V343A variant was exclusively observed in the Japanese population.Functionally impaired variants of COQ2 were associated with an increased risk of multiple-system atrophy in multiplex families and patients with sporadic disease, providing evidence of a role of impaired COQ2 activities in the pathogenesis of this disease. (Funded by the Japan Society for the Promotion of Science and others.). |
| تدمد: | 1533-4406 0028-4793 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::278e847779e0f61aaacdd8bf6c5654c5Test https://doi.org/10.1056/nejmoa1212115Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....278e847779e0f61aaacdd8bf6c5654c5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15334406 00284793 |
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