Park H J, Jang H, Kim J H, Lee J H, Shin H Y, Kim S M, Park K D, Yim S-V, Lee J H, Choi Y-C
Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
Clin Genet. 2017 Mar;91(3):403-410. doi: 10.1111/cge.12826. Epub 2016 Jul 29.
Inherited muscular disorders (IMDs) are clinically and genetically heterogeneous genetic disorders. We investigated the mutational spectrum and genotype-phenotype correlations in Korean patients with IMD. We developed a targeted panel of 69 known IMD genes and recruited a total of 209 Korean patients with IMD. Targeted capture sequencing identified 994 different variants. Among them, 98 variants were classified as pathogenic/likely pathogenic variants; 38 were novel variations. A total of 39 patients had the pathogenic/likely pathogenic variants. Among them, 75 (36%) patients were genetically confirmed, and 18 (9%) patients had one heterozygous variant of recessive myopathy. However, two genetically confirmed patients had an additional heterozygous variant of another recessive myopathy. Four patients with one heterozygous variant of a recessive myopathy showed different phenotypes, compared with the known phenotype of the identified gene. The major causative genes of Korean patients with IMDs were DMD (19 patients), COL6A1 (9), DYSF (9), GNE (7), LMNA (7), CAPN3 (6), and RYR1 (5). This study showed the mutational and clinical spectra in Korean patients with IMD and confirmed the usefulness of strategies utilizing targeted sequencing.
遗传性肌肉疾病（IMDs）是临床和遗传异质性的遗传疾病。我们研究了韩国IMD患者的突变谱以及基因型与表型的相关性。我们开发了一个包含69个已知IMD基因的靶向基因panel，并招募了总共209名韩国IMD患者。靶向捕获测序鉴定出994种不同的变异。其中，98种变异被分类为致病性/可能致病性变异；38种为新变异。共有39名患者携带致病性/可能致病性变异。其中，75名（36%）患者得到基因确诊，18名（9%）患者有一个隐性肌病的杂合变异。然而，两名基因确诊患者还有另一种隐性肌病的额外杂合变异。与已鉴定基因的已知表型相比，四名有一个隐性肌病杂合变异的患者表现出不同的表型。韩国IMD患者的主要致病基因是DMD（19例患者）、COL6A1（9例）、DYSF（9例）、GNE（7例）、LMNA（7例）、CAPN3（6例）和RYR1（5例）。本研究展示了韩国IMD患者的突变和临床谱，并证实了利用靶向测序策略的有效性。
