title: Target resequencing of neuromuscular disease-related genes using next-generation sequencing for patients with undiagnosed early-onset neuromuscular disorders.
abstract: Neuromuscular disorders are clinically and genetically heterogeneous diseases with broadly overlapping clinical features. Progress in molecular genetics has led to the identification of numerous causative genes for neuromuscular disorders, but Sanger sequencing-based diagnosis remains labor-intensive and expensive because the genes are large, the genotypes and phenotypes of neuromuscular disorders overlap and multiple genes related to a single phenotype exist. Recently, the advent of next-generation sequencing (NGS) has enabled efficient, concurrent examination of several related genes. Thus, we used NGS for target resequencing of neuromuscular disease-related genes from 42 patients in whom undiagnosed early-onset neuromuscular disorders. Causative genes were identified in 19/42 (45.2%) patients (six, congenital muscular dystrophy; two, Becker muscular dystrophy (BMD); three, limb-girdle muscular dystrophy; one, concurrent BMD and Fukuyama congenital muscular dystrophy; three, nemaline myopathy; one, centronuclear myopathy; one, congenital fiber-type disproportion; one, myosin storage myopathy; and one, congenital myasthenic syndrome). We detected variants of uncertain significance in two patients. In 6/19 patients who received a definitive diagnosis, the diagnosis did not require muscle biopsy. Thus, for patients with suspected neuromuscular disorders not identified using conventional genetic testing alone, NGS-based target resequencing has the potential to serve as a powerful tool that allows definitive diagnosis.
authors.affiliation: Affiliated Field of Medical Genetics, Division of Biomedical Engineering and Science, Graduate School of Tokyo Women's Medical University, Tokyo, Japan.|Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.|Department of Pediatrics, Imperial Gift Foundation AIIKU Maternal and Child Health Center, AIIKU Clinic, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kondo
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Urano
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Aoki
authors.affiliation: Affiliated Field of Medical Genetics, Division of Biomedical Engineering and Science, Graduate School of Tokyo Women's Medical University, Tokyo, Japan.|Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001706:Biopsy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009154:Mutation; D009468:Neuromuscular Diseases / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D010641:Phenotype; D015203:Reproducibility of Results; D055815:Young Adult