The CAPN3 p.Lys 254del variant is not always associated with dominant CAPN3-related muscular dystrophy

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dc.contributor.authorValls Rodríguez, Andrea
dc.contributor.authorGutiérrez Gutiérrez, Gerardo
dc.contributor.authorMartínez, Agustín
dc.contributor.authorRuiz Roldán, Cristina
dc.contributor.authorCamaño González, Pilar
dc.contributor.authorLópez de Munain Arregui, Adolfo
dc.contributor.authorSáenz, Amets
dc.date.accessioned2025-05-20T14:22:42Z
dc.date.available2025-05-20T14:22:42Z
dc.date.issued2024-02-01
dc.date.updated2025-05-20T14:22:42Z
dc.description.abstractIntroduction/Aims: Limb-girdle muscular dystrophy R1 (LGMDR1) calpain 3-related usually presents as a recessively transmitted weakness of proximal limb-girdle muscles due to pathogenic variants in the CAPN3 gene. Pathogenic variants in this gene have also been found in patients with an autosomal dominantly inherited transmission pattern (LGMDD4). The mechanism underlying this difference in transmission patterns has not yet been elucidated. Camptocormia, progressive limb weakness, myalgia, back pain, and increased CK levels are common clinical features associated with dominant forms. The p.Lys254del pathogenic variant was associated with camptocormia in two LGMDD4 families. This study aimed to present carriers found in recessively transmitted LGMDR1 families bearing the p.Lys254del variant that do not show muscle weakness. Methods: DNA sequencing was performed on exon 5 of CAPN3 in family members to establish the carrier status of the pathogenic variant. They were evaluated clinically and MRI was performed when available. Results: Two families presented with the p.Lys254del pathogenic variant in a homozygous or compound heterozygous state. Family members carrying only the pathogenic variant in the heterozygous state did not demonstrate the myopathic characteristics described in dominant patients. Camptocormia and other severe clinical symptoms were not observed. Discussion: We conclude that the p.Lys254del pathogenic variant per se cannot be solely responsible for camptocormia in dominant patients. Other undisclosed factors may regulate the phenotype associated with the dominant inheritance pattern in CAPN3 pathogenic variant carriers.en
dc.description.sponsorshipInstituto de Salud Carlos III (ISCIII), co-fundedby the European Union, Grant/Award Number: PI21/00047; Department of Health of the Government of the Basque Country, Grant/Award Number: 2021111022; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Grant/Award Number: CB06/05/1126; GENE (Association of Neuromuscular diseases of Gipuzkoa)en
dc.identifier.citationValls, A., Gutiérrez-Gutiérrez, G., Martínez, A., Ruiz-Roldán, C., Camaño, P., López de Munain, A., & Sáenz, A. (2024). The CAPN3 p.Lys 254del variant is not always associated with dominant CAPN3-related muscular dystrophy. Muscle and Nerve, 69(4), 472-476. https://doi.org/10.1002/MUS.28045
dc.identifier.doi10.1002/MUS.28045
dc.identifier.eissn1097-4598
dc.identifier.issn0148-639X
dc.identifier.urihttps://hdl.handle.net/20.500.14454/2786
dc.language.isoeng
dc.publisherJohn Wiley and Sons Inc
dc.rights© 2024 The Authors
dc.subject.otherCalpain 3, dominant inheritance pattern
dc.subject.otherCamptocormia
dc.subject.otherCANP3
dc.subject.otherLGMDD4
dc.subject.otherLGMDR1
dc.titleThe CAPN3 p.Lys 254del variant is not always associated with dominant CAPN3-related muscular dystrophyen
dc.typejournal article
dcterms.accessRightsopen access
oaire.citation.endPage476
oaire.citation.issue4
oaire.citation.startPage472
oaire.citation.titleMuscle and Nerve
oaire.citation.volume69
oaire.licenseConditionhttps://creativecommons.org/licenses/by-nc/4.0/
oaire.versionVoR
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