title: Discovery of pathogenic variants in a large Korean cohort of inherited muscular disorders.
abstract: 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.
authors.affiliation: Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.|Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Chemistry, Yonsei University, Seoul, Korea.
authors.forename: H
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: S M
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: K D
authors.initials: KD
authors.lastname: Park
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: S-V
authors.initials: SV
authors.lastname: Yim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Neurology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Choi
mesh_terms: D000328:Adult; D005260:Female; D056726:Genetic Association Studies; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010375:Pedigree; D056910:Republic of Korea
keywords: diagnosis; genotype-phenotype correlation; inherited muscular disorder; pathogenic variant; targeted sequencing