title: The de novo missense mutation N117S in skeletal muscle α‑actin 1 causes a mild form of congenital nemaline myopathy.
abstract: Nemaline myopathy (NM) constitutes a spectrum of primary skeletal muscle disorders, the diagnosis of which is based on muscle weakness and the visualization of nemaline bodies in muscle biopsies. Mutations in several NM causal genes have been attributed to the majority of NM cases, particularly mutations in nebulin and skeletal muscle α‑actin 1 (ACTA1), which are responsible for ~70% of cases; therefore, a genetic diagnostic strategy using targeted gene sequencing may potentially improve the diagnosis of suspected NM. The present study identified a de novo mutation in ACTA1 (c.350A>G; p.Asn117Ser) in a Chinese patient using target‑capture sequencing of a panel containing 125 known causal genes for inherited muscle diseases. Clinical analyses revealed that the case described in the present study exhibited a relatively mild phenotype with regards to muscle weakness, as compared with more severe phenotypes reported in several other patients with the same mutation, thus suggesting the existence of genetic modifiers. In conclusion, this approach may be helpful for the identification of clinically undiagnosed patients with highly heterogeneous disorders.
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Afﬁliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.affiliation: Physical Medicine and Rehabilitation Center, The Second Afﬁliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
mesh_terms: D000185:Actinin / Q000737:chemistry / Q000235:genetics*; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002648:Child; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D017696:Myopathies, Nemaline / Q000175:diagnosis* / Q000235:genetics*; D010641:Phenotype; D011487:Protein Conformation
chemical_list: C526905:ACTN1 protein, human; D000185:Actinin