LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation

Background: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of...

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Autores: Cesar, Sergi, Coll Vidal, Mònica, Fiol, Victoria, Fernández-Falgueras, Anna, Cruzalegui, José, Iglesias, Anna, Moll, Isaac, Perez-Serra, Alexandra, Martínez-Barrios, Estefanía, Ferrer Costa, Carles, Olmo, Bernat del, Puigmulé, Marta, Alcalde Masegu, Mireia, López López, Laura, Picó, Ferran, Berrueco, Rubén, Brugada Terradellas, Josep, Zschaeck, Irene, Natera-de Benito, Daniel, Carrera-García, Laura, Exposito-Escudero, Jessica, Ortez, Carlos, Nascimento, Andrés, Brugada, Ramon, Sarquella Brugada, Geòrgia, Campuzano Larrea, Oscar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/23013
Acceso en línea:http://hdl.handle.net/10256/23013
Access Level:acceso abierto
Palabra clave:Distròfia muscular -- Aspectes genètics
Muscular dystrophy -- Genetic aspects
Cromosomes humans -- Anomalies -- Diagnòstic
Human chromosome abnormalities -- Diagnosis
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spelling LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translationCesar, SergiColl Vidal, MònicaFiol, VictoriaFernández-Falgueras, AnnaCruzalegui, JoséIglesias, AnnaMoll, IsaacPerez-Serra, AlexandraMartínez-Barrios, EstefaníaFerrer Costa, CarlesOlmo, Bernat delPuigmulé, MartaAlcalde Masegu, MireiaLópez López, LauraPicó, FerranBerrueco, RubénBrugada Terradellas, JosepZschaeck, IreneNatera-de Benito, DanielCarrera-García, LauraExposito-Escudero, JessicaOrtez, CarlosNascimento, AndrésBrugada, RamonSarquella Brugada, GeòrgiaCampuzano Larrea, OscarDistròfia muscular -- Aspectes genèticsMuscular dystrophy -- Genetic aspectsCromosomes humans -- Anomalies -- DiagnòsticHuman chromosome abnormalities -- DiagnosisBackground: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA-related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences. Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA-related muscular dystrophy. Family members were also clinically assessed and genetically analyzed. Results: All patients carried a pathogenic rare variant in LMNA. Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA-related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA. Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes. Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progressionThis work was also supported by Obra Social. La Caixa Foundation (LCF/PR/GN16/50290001, and LCF/PR/GN19/50320002) and Instituto de Salud Carlos III, Fondo Investigación Sanitaria-FIS-(PI21/00094)Frontiers Media2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/23013http://hdl.handle.net/10256/23013Frontiers in Genetics, 2023, vol. 14, art. núm. 1135438Articles publicats (D-CM)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fgene.2023.1135438info:eu-repo/semantics/altIdentifier/eissn/1664-8021Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10256/230132026-05-29T05:05:01Z
dc.title.none.fl_str_mv LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
title LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
spellingShingle LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
Cesar, Sergi
Distròfia muscular -- Aspectes genètics
Muscular dystrophy -- Genetic aspects
Cromosomes humans -- Anomalies -- Diagnòstic
Human chromosome abnormalities -- Diagnosis
title_short LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
title_full LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
title_fullStr LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
title_full_unstemmed LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
title_sort LMNA-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation
dc.creator.none.fl_str_mv Cesar, Sergi
Coll Vidal, Mònica
Fiol, Victoria
Fernández-Falgueras, Anna
Cruzalegui, José
Iglesias, Anna
Moll, Isaac
Perez-Serra, Alexandra
Martínez-Barrios, Estefanía
Ferrer Costa, Carles
Olmo, Bernat del
Puigmulé, Marta
Alcalde Masegu, Mireia
López López, Laura
Picó, Ferran
Berrueco, Rubén
Brugada Terradellas, Josep
Zschaeck, Irene
Natera-de Benito, Daniel
Carrera-García, Laura
Exposito-Escudero, Jessica
Ortez, Carlos
Nascimento, Andrés
Brugada, Ramon
Sarquella Brugada, Geòrgia
Campuzano Larrea, Oscar
author Cesar, Sergi
author_facet Cesar, Sergi
Coll Vidal, Mònica
Fiol, Victoria
Fernández-Falgueras, Anna
Cruzalegui, José
Iglesias, Anna
Moll, Isaac
Perez-Serra, Alexandra
Martínez-Barrios, Estefanía
Ferrer Costa, Carles
Olmo, Bernat del
Puigmulé, Marta
Alcalde Masegu, Mireia
López López, Laura
Picó, Ferran
Berrueco, Rubén
Brugada Terradellas, Josep
Zschaeck, Irene
Natera-de Benito, Daniel
Carrera-García, Laura
Exposito-Escudero, Jessica
Ortez, Carlos
Nascimento, Andrés
Brugada, Ramon
Sarquella Brugada, Geòrgia
Campuzano Larrea, Oscar
author_role author
author2 Coll Vidal, Mònica
Fiol, Victoria
Fernández-Falgueras, Anna
Cruzalegui, José
Iglesias, Anna
Moll, Isaac
Perez-Serra, Alexandra
Martínez-Barrios, Estefanía
Ferrer Costa, Carles
Olmo, Bernat del
Puigmulé, Marta
Alcalde Masegu, Mireia
López López, Laura
Picó, Ferran
Berrueco, Rubén
Brugada Terradellas, Josep
Zschaeck, Irene
Natera-de Benito, Daniel
Carrera-García, Laura
Exposito-Escudero, Jessica
Ortez, Carlos
Nascimento, Andrés
Brugada, Ramon
Sarquella Brugada, Geòrgia
Campuzano Larrea, Oscar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Distròfia muscular -- Aspectes genètics
Muscular dystrophy -- Genetic aspects
Cromosomes humans -- Anomalies -- Diagnòstic
Human chromosome abnormalities -- Diagnosis
topic Distròfia muscular -- Aspectes genètics
Muscular dystrophy -- Genetic aspects
Cromosomes humans -- Anomalies -- Diagnòstic
Human chromosome abnormalities -- Diagnosis
description Background: Laminopathies are caused by rare alterations in LMNA, leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA-related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences. Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA-related muscular dystrophy. Family members were also clinically assessed and genetically analyzed. Results: All patients carried a pathogenic rare variant in LMNA. Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA-related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA. Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes. Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progression
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
peer-reviewed
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10256/23013
http://hdl.handle.net/10256/23013
url http://hdl.handle.net/10256/23013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fgene.2023.1135438
info:eu-repo/semantics/altIdentifier/eissn/1664-8021
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Frontiers in Genetics, 2023, vol. 14, art. núm. 1135438
Articles publicats (D-CM)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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