Current aspects and approaches to molecular diagnostics of hereditary neuromuscular diseases
- Authors: Fonova E.A.1, Zhalsanova I.Z.1, Skryabin N.A.1
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Affiliations:
- Research Institute of Medical Genetics, Tomsk National Research Medical Center
- Issue: Vol 28, No 2 (2024): CARDIOLOGY
- Pages: 282-292
- Section: MEDICAL GENETICS
- URL: https://journal-vniispk.ru/2313-0245/article/view/319767
- DOI: https://doi.org/10.22363/2313-0245-2024-28-1-282-292
- EDN: https://elibrary.ru/YZDACI
- ID: 319767
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Abstract
Relevance. The problem of diagnosing hereditary neuromuscular diseases is one of the most difficult in the medical specialists’ practice. Molecular genetic diagnostics is one of the fundamental aspects in the classification and subsequent approaches to the treatment and prevention of hereditary diseases. Pathogenic variants identification leads to the formation of separate subtypes and phenotypically identical diseases syndromes. This review examines modern diagnostic methods and algorithmization of patients with neuromuscular diseases. Despite enormous research and clinical efforts, the molecular causes remain unknown for almost half of patients with neuromuscular diseases due to genetic heterogeneity and molecular diagnostics based on a gene-by-gene approach. Next-generation sequencing (NGS) is an effective and cost-effective strategy for accelerating patient diagnosis. However, the diagnostic value of conducting and prescribing whole- exome or whole- genome sequencing is largely dependent on the clinical picture of the disease and the professional competence of the doctor. Hereditary neuromuscular diseases have similar initial symptoms, and molecular genetic diagnostics can pinpoint the cause and pathogenesis of the observed disorders in the patient. Conclusion . The molecular diagnostics algorithm is based on sequential analysis, starting with the search for the most common pathogenic variants using inexpensive and rapid methods, and progressing to the search for rare, previously undescribed pathogenic variants using whole-g enome/whole-exome studies. The phasing allows science and medicine to uncover previously unknown causes of severe disease in patients with neuromuscular diseases, which often leading to disability or premature death. Earlier genetic diagnosis should provide more effective treatment of the disease and better genetic counseling for families and will also allow access to pathogenetic therapy for neuromuscular diseases.
About the authors
Elizaveta A. Fonova
Research Institute of Medical Genetics, Tomsk National Research Medical Center
Author for correspondence.
Email: fonova.elizaveta@medgenetics.ru
ORCID iD: 0000-0002-1338-5451
SPIN-code: 5198-9456
Tomsk, Russian Federation
Irina Zh. Zhalsanova
Research Institute of Medical Genetics, Tomsk National Research Medical Center
Email: fonova.elizaveta@medgenetics.ru
ORCID iD: 0000-0001-6848-7749
SPIN-code: 9882-3730
Tomsk, Russian Federation
Nikolay A. Skryabin
Research Institute of Medical Genetics, Tomsk National Research Medical Center
Email: fonova.elizaveta@medgenetics.ru
ORCID iD: 0000-0002-2491-3141
SPIN-code: 3416-4105
Tomsk, Russian Federation
References
- Illarioshkin SN, Ivanova-Smolenskaya IA, Markova ED. DNA diagnostics and medical genetic counseling in neurology. M. Medical news agency. 2002. 591 p. (In Russian).
- Emery AEH. The muscular dystrophies. The Lancet. 2002;359(9307):687-695.
- Akhmedova PG, Zinchenko RA, Ugarov IV, Umakhanova ZR, Magomedova RM. Epidemiology of hereditary neuromuscular diseases in the Republic of Dagestan. Moscow. 2015. (In Russian).
- Rudenskaya GE, Kadnikova VA, Ryzhkova OP. Common forms of hereditary spastic paraplegia. Journal of Neurology and Psychiatry named after. CC Korsakov. 2019;119(2):94-104. (In Russian).
- Online Mendelian Inheritance in Man. An Online Catalog of Human Genes and Genetic Disorders. https://www.omim.org/, Access date 10/11/2023.
- Sharkova IV, Dadali EL. Clinical and genetic characteristics and algorithm for differential diagnosis of progressive muscular dystrophies that manifest after a period of normal motor development. Neuromuscular diseases. 2023;13(1):44-51. (In Russian).
- Swash M, Schwartz MS. Neuromuscular diseases: a practical approach to diagnosis and management. Springer Science & Business Media. 2013. 296 p.
- Efthymiou S, Manole A, Houlden H. Next-generation sequencing in neuromuscular diseases. Current opinion in neurology. 2016;29:527-536. doi: 10.1097/WCO.0000000000000374
- Passarge E. Color Atlas of Genetics. George Thieme Verlag Stuttgart. 4rd editions. New York. 2013. 481 p.
- Davidenkov SN. The problem of polymorphism of hereditary diseases of the nervous system. L. VIEM. 1934. 139 p. (In Russian).
- Rosenberg RN. An introduction to the molecular genetics of neurological disease: Recent advances. Archives of neurology. 1993;50(11):1123-1128. doi: 10.1001/archneur.1993.00540110005001
- Ivanova-Smolenskaya IA, Markova ED, Illarioshkin SN, Nikolskaya NN. Monogenic diseases of the central nervous system. In the book. Hereditary diseases of the nervous system. M.: Medicine. 1998. 104 p. (In Russian).
- Evtushenko SK, Shaimurzin MR, Evtushenko O. Neuromuscular diseases in children: problems of early diagnosis and modern medical and social rehabilitation. International Neurological Journal. 2013;5(59):15-35. (In Russian).
- Gusev EI, Konovalov AN, Gekht AB. Neurology. National leadership. Brief edition. M.: GEOTAR-Media. 2014. 688 p. (In Russian).
- Nallamilli BRR, Pan Y, King LS, Jagannathan L, Ramachander V, Lucas A, Markind J, Colzani R, Hegde M. Combined sequence and copy number analysis improves diagnosis of limb girdle and other myopathies. Annals of Clinical and Translational Neurology. 2023;10(11):2092-2104. doi: 10.1002/acn3.51896
- Arupova DR. Prevalence and nosological spectrum of neuromuscular diseases in various populations (literature review). Science, new technologies and innovations of Kyrgyzstan. 2016;7:72-75 (In Russian).
- Neuromuscular Disease Center. http://neuromuscular.wustl.edu
- Evtushenko K, Shaimurzin MR, Evtushenko O. Neuromuscular diseases in children: problems of early diagnosis and modern medical and social rehabilitation (scientific review and own observations). International Neurological Journal. 2013;5(59):13-31. (In Russian).
- Barp A, Mosca L, Sansone VA. Facilitations and hurdles of genetic testing in neuromuscular disorders. Diagnostics. 2021;11(4):701. doi.org/10.3390/diagnostics11040701
- Shaimurzin MR. New modified standards for diagnosis and treatment of myelino- and axonopathies in children with hereditary motor-sensory neuropathies (scientific review and personal observations). International Neurological Journal. 2012;1(47):11-21. (In Russian).
- Sitkali IV, Kolokolov OV, Lukina EV, Grigorieva EA, Popova OV. Polyneuropathies: clinical polymorphism and diagnostic algorithms. Saratov Medical Scientific Journal. 2016;12(2):292-296. (In Russian).
- Morozov AM, Sorokovikova TV, Minakova YuE, Belyak MA. Electroneuromyography: a modern view of the possibilities of application (literature review). Bulletin of the Medical Institute “Reaviz”: rehabilitation, doctor and health. 2022;3(57):107-116 (In Russian).
- Shieh PB. Advances in the Genetic Testing of Neuromuscular Diseases. Neurologic Clinics. 2020;38:519-528. doi: 10.1016/j.ncl.2020.03.012
- Volk AE, Kubisch C. The rapid evolution of molecular genetic diagnostics in neuromuscular diseases. Current Opinion in Neurology. 2017;30:523-528. doi: 10.1097/WCO.0000000000000478
- Harding AE. Clinical features and classification of inherited ataxias. Adv Neurol. 1993;61:1-14.
- Hekman KE, Gomez CM. The autosomal dominant spinocerebellar ataxias: emerging mechanistic themes suggest pervasive Purkinje cell vulnerability. Journal of Neurology, Neurosurgery & Psychiatry. 2015;86(5):554-561. doi: 10.1136/jnnp-2014-308421
- Di Donato S, Mariotti C, Taroni F. Spinocerebellar ataxia type 1. Handbook of clinical neurology. 2012;103:399-421.
- Fan HC, Ho LI, Chi CS, Chen SJ, Peng GS, Chan TM, Harn HJ. Polyglutamine (PolyQ) diseases: genetics to treatments. Cell transplantation. 2014;23(4-5):441-458. doi: 10.3727/096368914X67845
- Beecroft SJ, Yau KS, Allcock RJN, Mina K, Gooding R, Faiz F, Atkinson VJ, Wise C, Sivadorai P, Trajanoski D, Kresoje N, Ong R, Duff RM, Cabrera-Serrano M, Nowak KJ, Pachter N, Ravenscroft G, Lamont PJ, Davis MR, Laing NG. Targeted gene panel use in 2249 neuromuscular patients: The Australasian referral center experience. Ann. Clin. Transl. Neurol. 2020;7:353-362. doi.org/10.1002/acn3.51002
- Fernandez-Marmiesse A, Gouveia S, Couce ML. NGS Technologies as a Turning Point in Rare Disease Research, Diagnosis and Treatment. Curr.Med.Chem. 2018;25:404-432. doi: 10.2174/0929867324666170718101946
- Efthymiou S, Manole A, Houlden H. Next-generation sequencing in neuromuscular diseases. Curr. Opin. Neurol. 2016;29:527-536. doi: 10.1097/WCO.0000000000000374
- Di Resta C, Pipitone GB, Carrera P, Ferrari M. Current scenario of the genetic testing for rare neurological disorders exploiting next generation sequencing. Neural. Regen. Res. 2021;16:475-481. doi: 10.4103/1673-5374.293135
- Orengo JP, Murdock DR. Genetic Testing in Neuromuscular Disorders. Understanding ordering and interpretation of genetic tests is paramount for clinical management. Pract. Neurol. 2019;35-41.
- Montenegro G, Powell E, Huang J, Speziani F, Edwards YJ, Beecham G, Hulme W, Siskind C, Vance J, Shy M, Züchner S. Exome sequencing allows for rapid gene identification in a Charcot-Marie-Tooth family. Ann. Neurol. 2011;69:464-470. doi: 10.1002/ana.22235
- Mazzarotto F, Olivotto I, Walsh R Advantages and Perils of Clinical Whole-Exome and Whole-Genome Sequencing in Cardiomyopathy. Cardiovasc. Drugs. 2020;34:241-253. doi: 10.1007/s10557-020-06948-4
- Shchagina OA. Molecular basis of genetic heterogeneity and clinical variability of hereditary peripheral neuropathies. Moscow. 2023. MD Thesis. 383 p. (In Russian).
- Monies D, Alhindi HN, Almuhaizea MA, Abouelhoda M, Alazami AM, Goljan E, Alyounes B, Jaroudi D, Abdulelah A, Alabdulrahman K, Subhani S, El-Kalioby M, Faquih T, Wakil SM, Altassan NA, Meyer BF, Bohlega S. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies. Hum Genomics. 2016;10:32. doi: 10.1186/s40246-016-0089-8
- Schofield D, Alam K, Douglas L, Shrestha R, MacArthur DG, Davis M, Laing NG, Clarke NF, Burns J, Cooper ST, North KN, Sandaradura SA, O’Grady GL. Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases. NPJ Genom Med. 2017;2:4. doi: 10.1038/s41525-017-0006-7
- ACMG Board of Directors. Points to consider in the clinical application of genomic sequencing. Genet Med. 2012;14:759-761. https://doi.org/10.1038/gim.2012.74
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