Zaganas Ioannis, Mastorodemos Vasilios, Spilioti Martha, Mathioudakis Lambros, Latsoudis Helen, Michaelidou Kleita, Kotzamani Dimitra, Notas Konstantinos, Dimitrakopoulos Konstantinos, Skoula Irene, Ioannidis Stefanos, Klothaki Eirini, Erimaki Sophia, Stavropoulos Georgios, Vassilikos Vassilios, Amoiridis Georgios, Efthimiadis Georgios, Evangeliou Athanasios, Mitsias Panayiotis
Neurogenetics Laboratory, Medical School, University of Crete, Heraklion, Crete, Greece.
Neurology Department, University Hospital of Crete, Heraklion, Crete, Greece.
Mol Genet Metab Rep. 2020 Nov 30;25:100682. doi: 10.1016/j.ymgmr.2020.100682. eCollection 2020 Dec.
Inherited muscle disorders are caused by pathogenic changes in numerous genes. Herein, we aimed to investigate the etiology of muscle disease in 24 consecutive Greek patients with myopathy suspected to be genetic in origin, based on clinical presentation and laboratory and electrophysiological findings and absence of known acquired causes of myopathy. Of these, 16 patients (8 females, median 24 years-old, range 7 to 67 years-old) were diagnosed by Whole Exome Sequencing as suffering from a specific type of inherited muscle disorder. Specifically, we have identified causative variants in 6 limb-girdle muscular dystrophy genes (6 patients; , , , , , ), 3 metabolic myopathy genes (4 patients; , , ), 1 congenital myotonia gene (1 patient; ), 1 mitochondrial myopathy gene (1 patient; ) and 3 other myopathy-associated genes (4 patients; , , ). In 6 additional family members affected by myopathy, we reached genetic diagnosis following identification of a causative variant in an index patient. In our patients, genetic diagnosis ended a lengthy diagnostic process and, in the case of Multiple acyl-CoA dehydrogenase deficiency and Pompe's disease, it enabled specific treatment to be initiated. These results further expand the genotypic and phenotypic spectrum of inherited myopathies.
遗传性肌肉疾病由众多基因的致病性变化引起。在此，我们旨在基于临床表现、实验室检查和电生理检查结果以及排除已知的后天性肌病病因，对24例连续的疑似遗传性肌病的希腊患者进行肌肉疾病病因研究。其中，16例患者（8名女性，中位年龄24岁，范围7至67岁）通过全外显子测序被诊断患有特定类型的遗传性肌肉疾病。具体而言，我们在6个肢带型肌营养不良基因（6例患者； ， ， ， ， ， ）、3个代谢性肌病基因（4例患者； ， ， ）、1个先天性肌强直基因（1例患者； ）、1个线粒体肌病基因（1例患者； ）和3个其他肌病相关基因（4例患者； ， ， ）中鉴定出致病变异。在另外6名受肌病影响的家庭成员中，在索引患者中鉴定出致病变异后我们做出了基因诊断。在我们的患者中，基因诊断结束了漫长的诊断过程，并且在多种酰基辅酶A脱氢酶缺乏症和庞贝病的病例中，它使得能够开始进行特异性治疗。这些结果进一步扩展了遗传性肌病的基因型和表型谱。
