Panorama of the distal myopathies.
Panorama of the distal myopathies.
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DOI：
10.36185/2532-1900-028
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Udd B
中科院分区：
文献类型：
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作者：
Savarese M;Sarparanta J;Vihola A;Jonson PH;Johari M;Rusanen S;Hackman P;Udd B
远端肌病是一种遗传性原发性肌肉疾病，在发病时手和/或脚明显无力。发病年龄（从儿童早期到成年）、肌无力的分布（上肢与下肢）和组织学检查结果（从非特异性肌病变化到肌原纤维紊乱和镶边空泡）变化极大。然而，尽管远端肌病具有广泛的临床和遗传异质性，但它是肌营养不良症的一个类别：肌纤维进行性丢失的遗传性疾病。肌病性先天性关节弯曲也是一种远端肌病，通常由局灶性肌发育不全引起。大规模平行测序进一步扩展了与远端肌病相关的基因的长列表，并有助于鉴定更常与其他骨骼肌或心肌疾病相关的基因中的远端肌病致病罕见变异。目前，近20个基因（ACTN 2、CAV 3、NANAB、DNAJB 6、DNM 2、FLNC、HNRNPA 1、HSPB 8、KHLH 9、LDB 3、MATR 3、MB、MYOT、PLIN 4、TIA 1、VCP、NOTCH 2NLC、LRP 12、GIPS 1）与常染色体显性形式的远端肌病相关。四种基因（ADSSL，ANO 5，DYSF，GNE）的致病性变化导致常染色体隐性形式;五种基因（DES，MYH 7，NEB，RYR 1和TTN）的致病变体导致显性或隐性远端肌病。最后，一个双基因的机制，潜在的韦兰德样形式的远端肌病，最近已被阐明。SQSTM 1中罕见的致病性突变，以前被鉴定为骨疾病（佩吉特病），当与TIA 1中常见的多态性结合时，意外地导致远端肌病。本综述旨在描述远端肌病的遗传基础，并总结迄今为止所描述的不同形式的临床特征。
Distal myopathies are genetic primary muscle disorders with a prominent weakness at onset in hands and/or feet. The age of onset (from early childhood to adulthood), the distribution of muscle weakness (upper versus lower limbs) and the histological findings (ranging from nonspecific myopathic changes to myofibrillar disarrays and rimmed vacuoles) are extremely variable. However, despite being characterized by a wide clinical and genetic heterogeneity, the distal myopathies are a category of muscular dystrophies: genetic diseases with progressive loss of muscle fibers. Myopathic congenital arthrogryposis is also a form of distal myopathy usually caused by focal amyoplasia. Massive parallel sequencing has further expanded the long list of genes associated with a distal myopathy, and contributed identifying as distal myopathy-causative rare variants in genes more often related with other skeletal or cardiac muscle diseases. Currently, almost 20 genes (ACTN2, CAV3, CRYAB, DNAJB6, DNM2, FLNC, HNRNPA1, HSPB8, KHLH9, LDB3, MATR3, MB, MYOT, PLIN4, TIA1, VCP, NOTCH2NLC, LRP12, GIPS1) have been associated with an autosomal dominant form of distal myopathy. Pathogenic changes in four genes (ADSSL, ANO5, DYSF, GNE) cause an autosomal recessive form; and disease-causing variants in five genes (DES, MYH7, NEB, RYR1 and TTN) result either in a dominant or in a recessive distal myopathy. Finally, a digenic mechanism, underlying a Welander-like form of distal myopathy, has been recently elucidated. Rare pathogenic mutations in SQSTM1, previously identified with a bone disease (Paget disease), unexpectedly cause a distal myopathy when combined with a common polymorphism in TIA1. The present review aims at describing the genetic basis of distal myopathy and at summarizing the clinical features of the different forms described so far.