Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share By
Ryanodine Receptor Type 3 (Ryr3) As a Novel Gene Associated With a Myopathy With Nemaline Bodies Publisher Pubmed



Nilipour Y1 ; Nafissi S2 ; Tjust AE3, 4 ; Ravenscroft G5 ; Hossein Nejad Nedai H6 ; Taylor RL5 ; Varasteh V6 ; Pedrosa Domellof F3, 4 ; Zangi M7 ; Tonekaboni SH1 ; Olive M8 ; Kiiski K9 ; Sagath L9 ; Davis MR10 Show All Authors
Authors
  1. Nilipour Y1
  2. Nafissi S2
  3. Tjust AE3, 4
  4. Ravenscroft G5
  5. Hossein Nejad Nedai H6
  6. Taylor RL5
  7. Varasteh V6
  8. Pedrosa Domellof F3, 4
  9. Zangi M7
  10. Tonekaboni SH1
  11. Olive M8
  12. Kiiski K9
  13. Sagath L9
  14. Davis MR10
  15. Laing NG5
  16. Tajsharghi H5, 11

Source: European Journal of Neurology Published:2018


Abstract

Background and purpose: Nemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed with NEM, definitive mutations are not identified in the known genes, suggesting that there are other genes involved. This study describes compound heterozygosity for rare variants in ryanodine receptor type 3 (RYR3) gene in one such patient. Methods and 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 and subsarcolemmal areas, and within the cytoplasm. No likely pathogenic mutations in known NEM genes were identified. Copy number variation in known NEM genes was excluded by NEM-targeted comparative genomic hybridization array. Next-generation sequencing revealed compound heterozygous missense variants in the RYR3 gene. RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain and cauda equina samples. Immunofluorescence of human skeletal muscle revealed a ‘single-row’ appearance of RYR3, interspersed between the ‘double rows’ of ryanodine receptor type 1 (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. © 2018 EAN
Related Docs
View other Related Docs
1. Nemaline Myopathy: Reclassification of Previously Reported Variants According to Acmg Guidelines, and Report of Novel Genetic Variants, European Journal of Human Genetics (2023)
2. Sequential Targeted Exome Sequencing of 1001 Patients Affected by Unexplained Limb-Girdle Weakness, Genetics in Medicine (2020)
3. Colq-Related Congenital Myasthenic Syndrome: An Integrative View, Neurogenetics (2023)
Experts (# of related papers)
View all Related Experts
Shahriar Nafissi (5)
Gholamreza Zamani Ghalehtaki (2)
Other Related Docs
4. Expanding the Importance of Hmerf Titinopathy: New Mutations and Clinical Aspects, Journal of Neurology (2019)
5. Genetics of Gne Myopathy in the Non-Jewish Persian Population, European Journal of Human Genetics (2016)
6. Causative Variants Linked With Limb Girdle Muscular Dystrophy in an Iranian Population: 6 Novel Variants, Molecular Genetics and Genomic Medicine (2023)
7. Intellectual Disability, Muscle Weakness and Characteristic Face in Three Siblings: A Newly Described Recessive Syndrome Mapping to 3P24.3-P25.3, American Journal of Medical Genetics# Part A (2015)
8. Identification of a Compound Heterozygous Missense Mutation in Lama2 Gene From a Patient With Merosin-Deficient Congenital Muscular Dystrophy Type 1A, Journal of Clinical Laboratory Analysis (2021)
9. Dok7 Congenital Myasthenic Syndrome: Case Series and Review of Literature, BMC Neurology (2024)
10. A Novel Mutation in Alpha Sarcoglycan Gene in an Iranian Family With Limb Girdle Muscular Dystrophy 2D, Neurological Research (2016)
11. Identification of a Novel Asah1 Gene Mutation in Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy, Iranian Journal of Child Neurology (2024)
12. Autosomal Recessive Congenital Ichthyosis: Cers3 Mutations Identified by a Next Generation Sequencing Panel Targeting Ichthyosis Genes, European Journal of Human Genetics (2017)
13. Identifying Novel Agrn Variants in Congenital Myasthenic Syndrome: Insights From Three Iranian Families, Neuromuscular Disorders (2025)
14. A Case Report of Congenital Myasthenic Syndrome Caused by a Mutation in the Chrne Gene in the Iranian Population, Iranian Journal of Child Neurology (2020)
15. Expanding the Clinical Phenotype Associated With the Nin Gene; Report of a Patient With Short Stature, Microcephaly and Hearing Loss, Archives of Iranian Medicine (2025)
16. Clinical and Genetic Spectrum of a Large Cohort of Patients With Δ-Sarcoglycan Muscular Dystrophy, Brain (2022)
17. The First Comprehensive Cohort of the Duchenne Muscular Dystrophy in Iranian Population: Mutation Spectrum of 314 Patients and Identifying Two Novel Nonsense Mutations, Journal of Molecular Neuroscience (2020)
18. A Novel Heterozygous Missense Myh7 Mutation Potentially Causes an Autosomal Dominant Form of Myosin Storage Myopathy With Dilated Cardiomyopathy, BMC Cardiovascular Disorders (2023)
19. Report of Limb Girdle Muscular Dystrophy Type 2A in 6 Iranian Patients, One With a Novel Deletion in Capn3 Gene, Neuromuscular Disorders (2016)
20. First Report of Two Novel Mutations in Alpha Sarcoglycan Gene in Two Iranian Families With Lgmd, Genetics in the Third Millennium (2016)