{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:35:06Z","timestamp":1767926106429,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>LAMA2-associated muscular dystrophy is a rare genetic disorder caused by pathogenic or likely pathogenic variants in the LAMA2 gene. The aim of this study is to characterize the spectrum of pathogenic\/likely pathogenic variants in the LAMA2 gene among Russian patients, identify frequent pathogenic variants specific to this population, and estimate the prevalence of this disorder in Russia. Data were collected and analyzed from patients with confirmed diagnoses of LAMA2-associated muscular dystrophy using various molecular genetic methods in research centers from 2008 to 2024. Data were obtained from 90 unrelated patients with LAMA2-associated muscular dystrophy, out of which 83 presented with the more severe form, MDC1A1, while seven had milder form of LAMA2-associated muscular dystrophy. The most common pathogenic variants identified were nonsense mutations (40% of cases), followed by frameshift variants (29.3%), splicing variants (21.4%), gross deletions (5.3%), and missense variants (4%). It is worth noting that missense variants were found exclusively in patients with the milder form of LAMA2-associated muscular dystrophy. The most prevalent identified pathogenic variant was c.7536del (15%), characteristic of Slavic populations with an established founder effect. Additionally, a common pathogenic variant, c.8245-2A&gt;G, was found predominantly in Kazan Tatars. The estimated prevalence of LAMA2-associated muscular dystrophy in Russia is approximately 1 in 117,700.<\/jats:p>","DOI":"10.3390\/ijms26031257","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T10:14:30Z","timestamp":1738318470000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Spectrum of Pathogenic Variants in the LAMA2 Gene in the Russian Federation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0431-1477","authenticated-orcid":false,"given":"Polina","family":"Chausova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Cherevatova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-7378","authenticated-orcid":false,"given":"Aysylu","family":"Murtazina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8674-7230","authenticated-orcid":false,"given":"Maria","family":"Bulakh","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergei","family":"Kurbatov","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental Biology and Medicine, Voronezh State Medical University N.N. Burdenko, Voronezh 394036, Russia"},{"name":"Department of Neurology named after K.N. Tretyakov, Saratov State Medical University, Saratov 410000, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Anisimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya","family":"Kanivets","sequence":"additional","affiliation":[{"name":"Genomed LLC, Moscow 105005, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasilisa","family":"Udalova","sequence":"additional","affiliation":[{"name":"Genomed LLC, Moscow 105005, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Rudenskaya","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Demina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5819-4835","authenticated-orcid":false,"given":"Inna","family":"Sharkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Monakhova","sequence":"additional","affiliation":[{"name":"Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow 125412, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3998-3609","authenticated-orcid":false,"given":"Polina","family":"Tsygankova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":false,"given":"Oksana","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0351-1271","authenticated-orcid":false,"given":"Olga","family":"Shatohina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varvara","family":"Galkina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-8005","authenticated-orcid":false,"given":"Artem","family":"Borovikov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9092-6581","authenticated-orcid":false,"given":"Irina","family":"Mishina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-1303","authenticated-orcid":false,"given":"Olga","family":"Shchagina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Chukhrova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksander","family":"Polyakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115522, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yurchenco, P.D., and McKee, K.K. (2019). Linker Protein Repair of LAMA2 Dystrophic Neuromuscular Basement Membranes. Front. Mol. Neurosci., 12.","DOI":"10.3389\/fnmol.2019.00305"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sarkozy, A., Foley, A.R., Zambon, A.A., B\u00f6nnemann, C.G., and Muntoni, F. (2020). LAMA2-Related Dystrophies: Clinical Phenotypes, Disease Biomarkers, and Clinical Trial Readiness. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.00123"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/humu.23599","article-title":"LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-\u03b12 variome and its related phenotypes","volume":"39","author":"Oliveira","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.nmd.2004.06.009","article-title":"The congenital muscular dystrophies in 2004: A century of exciting progress","volume":"14","author":"Muntoni","year":"2004","journal-title":"Neuromuscul. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1002\/acn3.51172","article-title":"LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort","volume":"7","author":"Zambon","year":"2020","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1212\/01.WNL.0000138498.66940.7F","article-title":"LAMA2 loss-of-function mutation in a girl with a mild congenital muscular dystrophy","volume":"63","author":"Prandini","year":"2004","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"10","DOI":"10.17650\/2222-8721-2020-10-1-10-21","article-title":"Clinical and genetic characteristics of congenital muscular dystrophies (Part 1)","volume":"10","author":"Chausova","year":"2020","journal-title":"Neuromuscul. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.nmd.2013.12.011","article-title":"Members of International Standard of Care Committee for Congenital Muscular Dystrophies Diagnostic approach to the congenital muscular dystrophies","volume":"24","author":"Wang","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.nmd.2010.02.001","article-title":"Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations","volume":"20","author":"Geranmayeh","year":"2010","journal-title":"Neuromuscul. Disord."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1016\/j.nmd.2022.07.325","article-title":"FP.39 An international retrospective early natural history study of LAMA2-related dystrophies","volume":"32","author":"Orbach","year":"2022","journal-title":"Neuromuscul. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1093\/brain\/123.1.31","article-title":"Mutations in the laminin alpha2-chain gene in two children with early-onset muscular dystrophy","volume":"123","author":"Naom","year":"2000","journal-title":"Brain J. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/humu.10157","article-title":"Clinical and molecular study in congenital muscular dystrophy with partial laminin \u03b12 (LAMA2) deficiency","volume":"21","author":"Tezak","year":"2003","journal-title":"Hum. Mutat."},{"key":"ref_13","first-page":"101","article-title":"Novel Homozygous Pathogenic Mutations of LAMA 2 Gene in Patients with Congenital Muscular Dystrophy","volume":"15","author":"Khodaenia","year":"2021","journal-title":"Iran. J. Child Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3233\/JND-160151","article-title":"Targeted Re-Sequencing Emulsion PCR Panel for Myopathies: Results in 94 Cases","volume":"3","author":"Punetha","year":"2016","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1136\/jnnp-2020-325437","article-title":"Improving the efficacy of exome sequencing at a quaternary care referral centre: Novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases","volume":"92","author":"Grunseich","year":"2021","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.nmd.2020.03.009","article-title":"Clinical and genomic characteristics of LAMA2 related congenital muscular dystrophy in a patients\u2019 cohort from Qatar. A population specific founder variant","volume":"30","author":"Elsaid","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liang, W.-C., Tian, X., Yuo, C.-Y., Chen, W.-Z., Kan, T.-M., Su, Y.-N., Nishino, I., Wong, L.-J.C., and Jong, Y.-J. (2017). Comprehensive target capture\/next-generation sequencing as a second-tier diagnostic approach for congenital muscular dystrophy in Taiwan. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183406"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1007\/s00415-021-10806-0","article-title":"Diagnostic interest of whole-body MRI in early-and late-onset LAMA2 muscular dystrophies: A large international cohort","volume":"269","author":"Haberlova","year":"2022","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.mcp.2013.11.002","article-title":"High creatine kinase levels and white matter changes: Clinical and genetic spectrum of congenital muscular dystrophies with laminin alpha-2 deficiency","volume":"28","author":"Dekomien","year":"2014","journal-title":"Mol. Cell. Probes"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s13023-021-01950-x","article-title":"Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort","volume":"16","author":"Tan","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/cge.12366","article-title":"Genotype\/phenotype analysis in Chinese laminin-\u03b12 deficient congenital muscular dystrophy patients","volume":"87","author":"Xiong","year":"2015","journal-title":"Clin. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ge, L., Liu, A., Gao, K., Du, R., Ding, J., Mao, B., Hua, Y., Zhang, X., Tan, D., and Yang, H. (2018). Deletion of exon 4 in LAMA2 is the most frequent mutation in Chinese patients with laminin \u03b12-related muscular dystrophy. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-33098-3"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/j.1399-0004.2008.01068.x","article-title":"LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients","volume":"74","author":"Oliveira","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_24","first-page":"38","article-title":"Molecular genetic analysis of congenital merozin-negative muscular dystrophy in Russia","volume":"17","author":"Milovidova","year":"2018","journal-title":"Med. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3233\/JND-221552","article-title":"Estimating the Prevalence of LAMA2 Congenital Muscular Dystrophy using Population Genetic Databases","volume":"10","author":"Lake","year":"2023","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1212\/WNL.0000000000001303","article-title":"Prevalence of congenital muscular dystrophy in Italy","volume":"84","author":"Graziano","year":"2015","journal-title":"Neurology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0960-8966(99)00055-3","article-title":"Neuromuscular disorders in childhood: A descriptive epidemiological study from western Sweden","volume":"10","author":"Darin","year":"2000","journal-title":"Neuromuscul. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/sj.ejhg.5200743","article-title":"Merosin-deficient congenital muscular dystrophy, autosomal recessive (MDC1A, MIM#156225, LAMA2 gene coding for alpha2 chain of laminin)","volume":"10","author":"Allamand","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.nmd.2017.06.008","article-title":"Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period","volume":"27","author":"Sframeli","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/ana.24687","article-title":"Diagnosis and etiology of congenital muscular dystrophy: We are halfway there","volume":"80","author":"Lek","year":"2016","journal-title":"Ann. Neurol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1257\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:04Z","timestamp":1760027104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/3\/1257"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["ijms26031257"],"URL":"https:\/\/doi.org\/10.3390\/ijms26031257","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}