A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps
Por:
Segarra-Casas, A, Iruzubieta, P, Kapetanovic, S, Hernández-Laín, A, Jericó, I, Fernández-Torrón, R, Maneiro, M, Marco-Moreno, P, Zelaya-Huerta, MV, Rodríguez-Santiago, B, Calafell, F, Töpf, A, Straub, V, Vallejo-Illarramendi, A, de Munain, AL, Gallano, P, Gonzalez-Quereda, L
Publicada:
1 ene 2025
Resumen:
Background and purposePathogenic 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.MethodsFamilies 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.ResultsIndividuals 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.ConclusionHere, it is shown that the dominantly inherited p.Leu2286Val RYR1 founder variant is associated with a milder phenotype of exercise intolerance, myalgia and hyperCKemia.
Filiaciones:
Segarra-Casas, A:
Hosp Santa Creu & Sant Pau, St Quinti 77-79, Barcelona 08041, Spain
Univ Autonoma Barcelona, Genet & Microbiol Dept, Bellaterra, Spain
Iruzubieta, P:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Univ Deusto, Fac Engn, Bilbao, Spain
Kapetanovic, S:
Hosp Univ Basurto, ALS & Neuromuscular Unit, Dept Neurol, Bilbao, Spain
Biobizkaia Hlth Res Inst, Nucl Acid Therapeut Rare Disorders NAT RD, Baracaldo, Spain
Hernández-Laín, A:
Hosp Univ 12 Octubre, Neuropathol Unit, imas12, Res Inst, Madrid, Spain
Jericó, I:
Hosp Univ Navarra, Navarra Hlth Res Inst IdisNA, Dept Neurol, Neuromuscular & Motor Neuron Res Grp, Pamplona, Spain
Fernández-Torrón, R:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Univ Deusto, Fac Engn, Bilbao, Spain
Maneiro, M:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Marco-Moreno, P:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Zelaya-Huerta, MV:
Univ Hosp Navarra, Pathol Dept, Pamplona, Spain
Rodríguez-Santiago, B:
Hosp Santa Creu & Sant Pau, St Quinti 77-79, Barcelona 08041, Spain
Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Genome Instabil & DNA Repair Grp, Barcelona, Spain
Calafell, F:
CSIC, Inst Biol Evolut, Dept Med & Ciencies Vida, CSIC,UPF, Barcelona 08003, Spain
Töpf, A:
Newcastle Hosp NHS Fdn Trust, John Walton Muscular Dystrophy Res Ctr, Translat & Clin Res Inst, Newcastle Upon Tyne, England
Straub, V:
Newcastle Hosp NHS Fdn Trust, John Walton Muscular Dystrophy Res Ctr, Translat & Clin Res Inst, Newcastle Upon Tyne, England
Vallejo-Illarramendi, A:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Univ Basque Country UPV EHU, UPV EHU, Donostia San Sebastian, Spain
de Munain, AL:
Hosp Univ Donostia, Dept Neurol, Osakidetza Basque Hlth Serv, Donostia San Sebastian, Spain
Inst Salud Carlos III ISCIII, CIBERNED Ctr Invest Biomed Red Enfermedades Neurod, Madrid, Spain
Univ Deusto, Fac Engn, Bilbao, Spain
Univ Basque Country UPV EHU, Dept Neurosci, Donostia San Sebastian, Spain
Gallano, P:
Hosp Santa Creu & Sant Pau, St Quinti 77-79, Barcelona 08041, Spain
Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Gonzalez-Quereda, L:
Hosp Santa Creu & Sant Pau, St Quinti 77-79, Barcelona 08041, Spain
Inst Salud Carlos III, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain
Green Submitted, gold
|