Nemaline myopathies: a current view
Nemaline myopathies: a current view
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DOI：
10.1007/s10974-019-09519-9
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发表时间：
2019-06-01
影响因子：
2.7
通讯作者：
Wallgren-Pettersson, Carina
中科院分区：
文献类型：
--
作者：
Sewry, Caroline A.;Laitila, Jenni M.;Wallgren-Pettersson, Carina
线状体肌病是由至少12个基因中的新生、显性或隐性遗传突变引起的一组异质性先天性肌病。编码骨骼α-肌动蛋白（ACTA 1）和星云蛋白（NEB）的基因是最常见的遗传原因。大多数患者具有以肌无力和张力减退为特征的先天性发病，但临床表型谱很广，从严重的新生儿表现到儿童期较轻疾病的发病。大多数成人发病的患者具有进行性病程的自身免疫相关性肌病。大规模平行测序方法的广泛应用正在增加已知致病基因的数量并拓宽临床表型的范围。线状体肌病通过电子显微镜下杆状或卵圆形结构的存在以及光学显微镜下用改良的Gomori三色技术染成红色来鉴定。这些杆状体或线状体来源于Z线（也称为Z盘或Z盘），具有相似的晶格结构和蛋白质含量。在KLHL 40和LMOD 3突变的患者中，它们的形状是独特的，可以用于诊断。线虫体的数量和分布在纤维和不同肌肉之间变化，但与严重程度或预后无关。其他病理特征，如帽，核心和纤维类型不比例与已知导致杆存在的相同基因相关。动物模型正在推进对不同基因中各种突变的影响的理解，并为开发治疗方法铺平道路，这些治疗方法目前仅管理症状，旨在维持肌肉力量，关节活动，截肢，呼吸和日常生活活动的独立性。
Nemaline myopathies are a heterogenous group of congenital myopathies caused by de novo, dominantly or recessively inherited mutations in at least twelve genes. The genes encoding skeletal alpha-actin (ACTA1) and nebulin (NEB) are the commonest genetic cause. Most patients have congenital onset characterized by muscle weakness and hypotonia, but the spectrum of clinical phenotypes is broad, ranging from severe neonatal presentations to onset of a milder disorder in childhood. Most patients with adult onset have an autoimmune-related myopathy with a progressive course. The wide application of massively parallel sequencing methods is increasing the number of known causative genes and broadening the range of clinical phenotypes. Nemaline myopathies are identified by the presence of structures that are rod-like or ovoid in shape with electron microscopy, and with light microscopy stain red with the modified Gomori trichrome technique. These rods or nemaline bodies are derived from Z lines (also known as Z discs or Z disks) and have a similar lattice structure and protein content. Their shape in patients with mutations in KLHL40 and LMOD3 is distinctive and can be useful for diagnosis. The number and distribution of nemaline bodies varies between fibres and different muscles but does not correlate with severity or prognosis. Additional pathological features such as caps, cores and fibre type disproportion are associated with the same genes as those known to cause the presence of rods. Animal models are advancing the understanding of the effects of various mutations in different genes and paving the way for the development of therapies, which at present only manage symptoms and are aimed at maintaining muscle strength, joint mobility, ambulation, respiration and independence in the activities of daily living.