The genetics and pathology of mitochondrial disease.
The genetics and pathology of mitochondrial disease.
复制标题
DOI：
10.1002/path.4809
复制
发表时间：
2017-01
影响因子：
7.3
通讯作者：
Taylor, Robert W.
中科院分区：
文献类型：
--
作者：
Alston, Charlotte L.;Rocha, Mariana C.;Lax, Nichola Z.;Turnbull, Doug M.;Taylor, Robert W.
关键词：
线粒体是双膜结合细胞器，存在于所有有核真核细胞中，负责以ATP形式产生细胞能量。线粒体功能受到双重遗传控制——16.6 kb的线粒体基因组，只有37个基因，以及编码线粒体蛋白质组中剩余的约1300个蛋白质的核基因组。线粒体功能障碍可由线粒体DNA或核线粒体基因缺陷引起，并可在儿童期或成人期出现，伴有巨大的临床异质性，症状可影响单个器官或组织，或累及多系统。绝大多数线粒体疾病患者无法治愈线粒体疾病，因此基因诊断对于遗传咨询和复发风险计算至关重要，并可能影响受影响患者的临床管理。新一代测序策略在发现新的疾病基因和诊断临床受影响的患者中被证明是关键的；bbbb250基因的突变现已被证明可引起线粒体疾病，这些患者的生化、组织化学、免疫细胞化学和神经病理学特征导致了诊断测试策略的改进和新的诊断技术。这篇综述的重点是目前与线粒体疾病相关的遗传景观，然后重点研究两个临床相关器官-骨骼肌和大脑的相关线粒体病理学进展。©2016作者。由John Wiley & Sons Ltd代表大不列颠和爱尔兰病理学会出版的病理学杂志。
Mitochondria are double‐membrane‐bound organelles that are present in all nucleated eukaryotic cells and are responsible for the production of cellular energy in the form of ATP. Mitochondrial function is under dual genetic control – the 16.6‐kb mitochondrial genome, with only 37 genes, and the nuclear genome, which encodes the remaining ∼1300 proteins of the mitoproteome. Mitochondrial dysfunction can arise because of defects in either mitochondrial DNA or nuclear mitochondrial genes, and can present in childhood or adulthood in association with vast clinical heterogeneity, with symptoms affecting a single organ or tissue, or multisystem involvement. There is no cure for mitochondrial disease for the vast majority of mitochondrial disease patients, and a genetic diagnosis is therefore crucial for genetic counselling and recurrence risk calculation, and can impact on the clinical management of affected patients. Next‐generation sequencing strategies are proving pivotal in the discovery of new disease genes and the diagnosis of clinically affected patients; mutations in >250 genes have now been shown to cause mitochondrial disease, and the biochemical, histochemical, immunocytochemical and neuropathological characterization of these patients has led to improved diagnostic testing strategies and novel diagnostic techniques. This review focuses on the current genetic landscape associated with mitochondrial disease, before focusing on advances in studying associated mitochondrial pathology in two, clinically relevant organs – skeletal muscle and brain. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
登录
查看更多内容
影响因子：
3.5
作者：
Angebault, Claire;Charif, Majida;Roubertie, Agathe
通讯作者：
Roubertie, Agathe
影响因子：
30.8
作者：
Bourdon, Alice;Minai, Limor;Rotig, Agnes
通讯作者：
Rotig, Agnes
影响因子：
29
作者：
Balsa, Eduardo;Marco, Ricardo;Antonio Enriquez, Jose
通讯作者：
Antonio Enriquez, Jose
影响因子：
4
作者：
Alston CL;Davison JE;Meloni F;van der Westhuizen FH;He L;Hornig-Do HT;Peet AC;Gissen P;Goffrini P;Ferrero I;Wassmer E;McFarland R;Taylor RW
通讯作者：
Taylor RW
影响因子：
9.8
作者：
Antonicka, H;Mattman, A;Shoubridge, EA
通讯作者：
Shoubridge, EA