Research Centre for Medical Genetics, Moscow, Russia.
Clin Genet. 2022 Dec;102(6):465-473. doi: 10.1111/cge.14216. Epub 2022 Sep 6.
Dysferlinopathies are a clinically heterogeneous group of diseases caused by mutations in the DYSF gene encoding the dysferlin protein. Dysferlin is mostly expressed in muscle tissues and is localized in the sarcolemma, where it performs its main function of resealing and maintaining of the integrity of the cell membrane. At least four forms of dysferlinopathies have been described: Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, distal myopathy with anterior tibial onset, and isolated hyperCKemia. Here we review the clinical features of different forms of dysferlinopathies and attempt to identify genotype-phenotype correlations. Because of the great clinical variability and rarety of the disease and mutations little is known, how different phenotypes develop as a result of different mutations. However, missense mutations seem to induce more severe disease than LoF, which is typical for many muscle dystrophies. The role of several specific mutations and possible gene modifiers is also discussed in the paper.
肌营养不良蛋白病是一组由 DYSF 基因突变引起的临床表现异质性疾病，该基因编码肌营养不良蛋白。肌营养不良蛋白主要在肌肉组织中表达，定位于肌膜，在那里它发挥其主要功能，即修复和维持细胞膜的完整性。已经描述了至少四种形式的肌营养不良蛋白病：肌病、肢带型肌营养不良 2B 型、胫骨前肌起始的远端肌病和孤立性高肌酸激酶血症。在这里，我们回顾了不同形式的肌营养不良蛋白病的临床特征，并试图确定基因型-表型相关性。由于疾病和突变的罕见性以及临床表现的高度变异性，目前还不太清楚不同的表型是如何由不同的突变引起的。然而，错义突变似乎比肌营养不良症中常见的无义突变导致更严重的疾病。本文还讨论了几种特定突变和可能的基因修饰物的作用。
