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: Eri Kondo, Takafumi Nishimura, Tomoki Kosho, Yuji Inaba, Satomi Mitsuhashi, Takefumi Ishida, Atsushi Baba, Kenichi Koike, Ichizo Nishino, Ikuya Nonaka, Toru Furukawa, Kayoko Saito
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 158A Issue 4 Pg. 772-8 (Apr 2012) ISSN: 1552-4833 [Electronic] United States
• PMID: 22407809 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Ryanodine Receptor Calcium Release Channel

Topics

• Base Sequence
• Child, Preschool
• DNA Mutational Analysis
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Muscle Fibers, Skeletal (pathology)
• Muscle Hypotonia (genetics, pathology)
• Mutation
• Myopathies, Nemaline (genetics, pathology)
• Ophthalmoplegia (genetics)
• Ryanodine Receptor Calcium Release Channel (genetics)