Department of Physical Medicine and Rehabilitation, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Clin Chim Acta. 2020 Jul;506:50-54. doi: 10.1016/j.cca.2020.03.021. Epub 2020 Mar 14.
Emery-Dreifuss muscular dystrophy (EDMD) also known as humeroperoneal muscular dystrophy, is a skeletal myopathy characterized by the clinical triad of progressive muscular weakness, joint contractures, and cardiac disease.
Herein, we reported a family including two patients (the proband and his son) affected with progressive muscular dystrophy manifested by joint contractures without cardiac involvement ("EDMD-like" phenotype). Interestingly, electodiagnostic study results of the proband showed a neuropathic pattern different from the myopathic pattern in most muscular dystrophy patients. To identify the underlying genetic cause, genomic DNA of the proband was analyzed by WES using Agilent's SureSelect XT Human All Exon v5.
A novel de novo pathogenic heterozygous missense mutation (NM_182914.2: c.4858G > A; p.Ala1620Thr) of the SYNE2 gene, which had not been previously reported was identified by whole exome sequencing in the proband and by Sanger sequencing in his son.
To the best knowledge, SYNE2 mutation was reported first by whole exome sequencing in a Korean family with EDMD-like features. We emphasized the role of genetic analysis using whole exome sequencing, which allows the correct recognition of this molecular diagnosis and brings together the neuromuscular spectrum of this complex clinical scenario, leading to proper clinical management.
先天性肌营养不良症（EDMD）也称为肱二头肌腓肠肌营养不良症，是一种骨骼肌病，其特征为进行性肌无力、关节挛缩和心脏病的三联征。
本文报告了一个家系，包括两名患者（先证者及其儿子），他们患有进行性肌营养不良症，表现为关节挛缩而无心脏受累（“EDMD 样”表型）。有趣的是，先证者的电诊断研究结果显示出一种不同于大多数肌营养不良症患者的肌病模式的神经病变模式。为了确定潜在的遗传原因，使用 Agilent 的 SureSelect XT Human All Exon v5 通过 WES 对先证者的基因组 DNA 进行了分析。
通过对先证者进行全外显子测序，在其儿子中进行 Sanger 测序，发现了一个以前未报道过的 SYNE2 基因的新型从头致病性杂合错义突变（NM_182914.2：c.4858G>A；p.Ala1620Thr）。
据我们所知，SYNE2 突变是通过全外显子测序首次在一个具有 EDMD 样特征的韩国家族中报道的。我们强调了使用全外显子测序进行遗传分析的作用，这可以正确识别这种分子诊断，并将这种复杂临床情况的神经肌肉谱联系起来，从而进行适当的临床管理。
