Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
Am J Med Genet A. 2012 Apr;158A(4):772-8. doi: 10.1002/ajmg.a.35243. Epub 2012 Mar 9.
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.
肌强直性营养不良（Nemaline myopathy，NM）是一组先天性肌病，其特征是骨骼肌纤维的肌浆中存在独特的杆状包涵体“肌原纤维”。迄今为止，已经发现 ACTA1、NEB、TPM3、TPM2、TNNT1 和 CFL2 可导致 NM。我们通过使用靶向基因捕获的高通量测序对先天性肌病/肌营养不良相关基因进行筛选，在一位严重先天性 NM 患者中发现了隐性 RYR1 突变。该患者表现为胎儿运动不能、新生儿严重肌无力伴低张力、呼吸功能不全、吞咽障碍和眼肌瘫痪。骨骼肌组织学显示存在杆状体和小的 I 型纤维，但没有中央核或微小核。先天性肌病是一组分子、组织病理学和临床表现异质性的疾病，被认为是高通量测序的一个很好的候选对象。
