A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps

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dc.contributor.authorSegarra Casas, Alba
dc.contributor.authorIruzubieta Agudo, Pablo
dc.contributor.authorKapetanovic García, Solange
dc.contributor.authorHernández Laín, A.
dc.contributor.authorJericó Pascual, Ivonne
dc.contributor.authorFernández Torrón, Roberto
dc.contributor.authorManeiro, Miren
dc.contributor.authorMarco Moreno, Pablo
dc.contributor.authorZelaya Huerta, María Victoria
dc.contributor.authorRodríguez Santiago, Benjamín
dc.contributor.author Calafell Majó, Francesc
dc.contributor.authorTöpf, Ana
dc.contributor.authorStraub, Volker
dc.contributor.authorVallejo Illarramendi, Ainara
dc.contributor.authorLópez de Munain Arregui, Adolfo
dc.contributor.authorGallano Petit, María Pía
dc.contributor.authorGonzález Quereda, Lidia
dc.date.accessioned2025-02-13T15:38:43Z
dc.date.available2025-02-13T15:38:43Z
dc.date.issued2025-01
dc.date.updated2025-02-13T15:38:43Z
dc.description.abstractBackground and purpose: Pathogenic variants in the RYR1 gene have been associated with a variety of conditions, ranging from congenital myopathy to adult manifestations. Our aim was to characterize the p.Leu2286Val variant in 17 Basque patients, to accurately determine its correlation with clinical features and to explore the possible founder effect of the variant. Methods: Families harbouring the p.Leu2286 RYR1 variant underwent a detailed clinical evaluation, including muscle magnetic resonance imaging, electromyography and muscle biopsy. Haplotypes were analysed in available patients and their relatives. Results: Individuals carrying the p.Leu2286Val shared a common haplotype, suggesting a founder event in the Basque Country population. The most prevalent features were exertional myalgia, high creatine kinase (CK) levels, cramps and muscle hypertrophy. None of the patients carrying only the p.Leu2286Val showed progression to severe muscle weakness and muscle magnetic resonance imaging showed a heterogeneous muscle involvement. Muscle biopsy revealed non-specific findings in two patients and features associated with central core disease in one patient carrying only the p.Leu2286Val and two patients harbouring an additional RYR1 variant. Three individuals carrying an in trans RYR1 variant presented with an earlier onset and more severe phenotype. Conclusion: Here, it is shown that the dominantly inherited p.Leu2286Val RYR1 founder variant is associated with a milder phenotype of exercise intolerance, myalgia and hyperCKemia.en
dc.description.sponsorshipMinisterio de Universidades, Grant/Award Number: FPU20/06692; Fundacion Jesus De Gangoiti Barrera; Instituto de Salud Carlos III, Grant/Award Number: MCIN/AEI/10.13039/501100011033, PI18/01585 and PI22/01859; Eusko Jaurlaritza, Grant/Award Number: 2022111045 and GIU20/057; Limb Girdle Muscular Dystrophy 2i Research Fund; CureLGMD2i; Sanofi Genzyme; Ultragenyx Pharmaceutical; LGMD2D Foundation; Kurt+Peter Foundationen
dc.identifier.citationSegarra-Casas, A., Iruzubieta, P., Kapetanovic, S., Hernández-Laín, A., Jericó, I., Fernández-Torrón, R., Maneiro, M., Marco-Moreno, P., Zelaya-Huerta, M. V., Rodríguez-Santiago, B., Calafell, F., Töpf, A., Straub, V., Vallejo-Illarramendi, A., López de Munain, A., Gallano, P., & Gonzalez-Quereda, L. (2025). A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps. European Journal of Neurology, 32(1). https://doi.org/10.1111/ENE.16471
dc.identifier.doi10.1111/ENE.16471
dc.identifier.eissn1468-1331
dc.identifier.issn1351-5101
dc.identifier.urihttp://hdl.handle.net/20.500.14454/2296
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.rights© 2024 The Author(s)
dc.subject.otherExercise intolerance
dc.subject.otherHyperCKemia
dc.subject.otherMyalgia
dc.subject.otherRYR1-related myopathies
dc.titleA founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle crampsen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.issue1
oaire.citation.titleEuropean Journal of Neurology
oaire.citation.volume32
oaire.licenseConditionhttps://creativecommons.org/licenses/by-nc-nd/4.0/
oaire.versionVoR
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