title: Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing.
abstract: Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions "nemaline bodies" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM. We have identified recessive RYR1 mutations in a patient with severe congenital NM, through high-throughput screening of congenital myopathy/muscular dystrophy-related genes using massively parallel sequencing with target gene capture. The patient manifested fetal akinesia, neonatal severe hypotonia with muscle weakness, respiratory insufficiency, swallowing disturbance, and ophthalomoplegia. Skeletal muscle histology demonstrated nemaline bodies and small type 1 fibers, but without central cores or minicores. Congenital myopathies, a molecularly, histopathologically, and clinically heterogeneous group of disorders are considered to be a good candidate for massively parallel sequencing.
authors.affiliation: Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Kondo
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kosho
authors.forename: Yuji
authors.initials: Y
authors.lastname: Inaba
authors.forename: Satomi
authors.initials: S
authors.lastname: Mitsuhashi
authors.forename: Takefumi
authors.initials: T
authors.lastname: Ishida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Baba
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Toru
authors.initials: T
authors.lastname: Furukawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Saito
mesh_terms: D001483:Base Sequence; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009123:Muscle Hypotonia / Q000235:genetics / Q000473:pathology; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology*; D009886:Ophthalmoplegia / Q000235:genetics*; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel