Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul 34390, Turkey.
Intergen Genetic Center, Ankara, Turkey.
Neuromuscul Disord. 2022 Sep;32(9):718-727. doi: 10.1016/j.nmd.2022.07.397. Epub 2022 Jul 13.
Emery-Dreifuss muscular dystrophy (EDMD) is a rare inherited disorder usually presenting in childhood with early contractures, slowly progressive scapulohumeroperoneal weakness/atrophy and potentially fatal dilated cardiomyopathy with conduction defects. We evaluated clinical and genetic findings of 32 patients with EDMD phenotype from 14 unrelated families, diagnosed at the Department of Neurology, Istanbul Faculty of Medicine between 1989 and 2022. Twenty-three patients from 8 unrelated families were diagnosed with EDMD1 (58%), 5 patients from 3 families with EDMD2 (21%), and 2 patients from 1 family with the rare EDMD3 (7%). Genetic diagnosis was achieved in 12 unrelated kinships with classical EDMD phenotype (86%) by applying panel testing, but no mutation could be determined in 2 patients with classical EDMD phenotype from 2 unrelated families (14%). Three novel pathogenic variants (c.19delC, c.416_417delTT, c.123C > G) in EMD, and a novel (c.1441dupT) heterozygous likely pathogenic variant in LMNA gene were found. This is the largest cohort from Turkey, expanding the genetic spectrum of EDMD, and providing clues for genetic testing of EDMD in Turkey.
先天性肌营养不良症 1D(Emery-Dreifuss muscular dystrophy 1D,EDMD1)是一种罕见的遗传性疾病,通常在儿童期发病,表现为早期挛缩、进行性肩胛带肱二头肌无力/萎缩和潜在致命的扩张型心肌病伴传导缺陷。我们评估了 1989 年至 2022 年期间在伊斯坦布尔医学院神经病学系诊断的 14 个无关家庭的 32 例 EDMD 表型患者的临床和遗传发现。8 个无关家庭的 23 例患者被诊断为 EDMD1(58%),3 个家庭的 5 例患者被诊断为 EDMD2(21%),1 个家庭的 2 例患者被诊断为罕见的 EDMD3(7%)。通过应用面板检测,在 12 个具有典型 EDMD 表型的无关亲属中实现了基因诊断(86%),但在 2 个具有典型 EDMD 表型的无关家庭的 2 例患者中无法确定突变(14%)。在 EMD 中发现了 3 个新的致病性变异(c.19delC、c.416_417delTT、c.123C>G),在 LMNA 基因中发现了 1 个新的(c.1441dupT)杂合可能致病性变异。这是来自土耳其的最大队列,扩展了 EDMD 的遗传谱,并为土耳其的 EDMD 基因检测提供了线索。