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Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies
Pediatric Pathology Research Centre, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Iran.
Department of Neurology, Tehran University of Medical Sciences, Iran.
Department of Integrative Medical Biology, Umeå University, Sweden / Department of Clinical Sciences, Umeå University, Sweden.
Centre for Medical Research, The University of Western Australia and the Harry Perkins Institute for Medical Research, Nedlands, Western Australia, Australia.
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2018 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed) Published
Abstract [en]

Background: Nemaline myopathy has been associated with mutations in twelve genes to date. However, for some patients diagnosed with nemaline myopathy, definitive mutations are not identified in the known genes, suggesting there are other genes involved. This study describes compound heterozygosity for rare variants in RYR3 in one such patient.

Results: Clinical examination of the patient at 22 years of age revealed a long-narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear areas, subsarcolemmal and within the cytoplasm. No likely pathogenic mutations in known nemaline myopathy genes were identified. Copy number variation in known nemaline myopathy genes was excluded by nemaline myopathy targeted array-CGH. Next generation sequencing revealed compound heterozygous missense variants in the ryanodine receptor type 3 gene (RYR3).  RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain or cauda equina samples. Immunofluorescence of human skeletal muscle revealed a "single-row" appearance of RYR3, interspaced between the "double-rows" of RYR1 at each A-I junction.

Conclusion: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

Place, publisher, year, edition, pages
Blackwell Publishing, 2018. Vol. 25, no 6, p. 841-847
Keywords [en]
RYR3, intracellular Ca2+ channels, nemaline myopathy, ryanodine receptors
National Category
Medical and Health Sciences Genetics Medical Genetics Neurology
Research subject
Biomedical Genetics; Translational Medicine TRIM
Identifiers
URN: urn:nbn:se:his:diva-14955DOI: 10.1111/ene.13607ISI: 000431989200012PubMedID: 29498452Scopus ID: 2-s2.0-85044433098OAI: oai:DiVA.org:his-14955DiVA, id: diva2:1189597
Funder
Swedish Research CouncilEU, FP7, Seventh Framework ProgrammeAvailable from: 2018-03-12 Created: 2018-03-12 Last updated: 2018-05-25Bibliographically approved

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Tajsharghi, Homa

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