Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy

Detalhes bibliográficos
Autor(a) principal: Dourado Junior, Mário Emílio Teixeira
Data de Publicação: 2021
Outros Autores: Perez, Jorge Alonso, Quereda, Lidia Gonzalez, et, al
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/handle/123456789/54166
http://dx.doi.org/10.1093/brain/awab301
Resumo: Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease’s severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.
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spelling Dourado Junior, Mário Emílio TeixeiraPerez, Jorge AlonsoQuereda, Lidia Gonzalezet, alhttps://orcid.org/0000-0002-9462-22942023-07-25T20:17:28Z2023-07-25T20:17:28Z2021ALONSO-PÉREZ, Jorge; GONZÁLEZ-QUEREDA, Lidia; BRUNO, Claudio; PANICUCCI, Chiara; ALAVI, Afagh; NAFISSI, Shahriar; NILIPOUR, Yalda; ZANOTELI, Edmar; ISIHI, Lucas Michielon de Augusto; MELEGH, Béla. Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy. Brain, [S.L.], v. 145, n. 2, p. 596-606, 13 set. 2021. Oxford University Press (OUP). http://dx.doi.org/10.1093/brain/awab301. Disponível em: https://academic.oup.com/brain/article/145/2/596/6369509?login=true. Acesso em: 13 jul. 2023.https://repositorio.ufrn.br/handle/123456789/54166http://dx.doi.org/10.1093/brain/awab301BrainAttribution 3.0 Brazilhttp://creativecommons.org/licenses/by/3.0/br/info:eu-repo/semantics/openAccessmuscular dystrophiesdelta-sarcoglycanSGCDLGMD-R6/2F ( limb-girdle muscular dystrophies)Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease’s severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.engreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNORIGINALClinicalGeneticSpectrum_DouradoJr_2021.pdfClinicalGeneticSpectrum_DouradoJr_2021.pdfapplication/pdf1062978https://repositorio.ufrn.br/bitstream/123456789/54166/1/ClinicalGeneticSpectrum_DouradoJr_2021.pdfdc4b472044783b64af92e772c7c2d9bfMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8914https://repositorio.ufrn.br/bitstream/123456789/54166/2/license_rdf4d2950bda3d176f570a9f8b328dfbbefMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/54166/3/license.txte9597aa2854d128fd968be5edc8a28d9MD53123456789/541662023-07-25 17:17:28.672oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2023-07-25T20:17:28Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.pt_BR.fl_str_mv Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
title Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
spellingShingle Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
Dourado Junior, Mário Emílio Teixeira
muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
title_short Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
title_full Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
title_fullStr Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
title_full_unstemmed Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
title_sort Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
author Dourado Junior, Mário Emílio Teixeira
author_facet Dourado Junior, Mário Emílio Teixeira
Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
author_role author
author2 Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
author2_role author
author
author
dc.contributor.authorID.pt_BR.fl_str_mv https://orcid.org/0000-0002-9462-2294
dc.contributor.author.fl_str_mv Dourado Junior, Mário Emílio Teixeira
Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
dc.subject.por.fl_str_mv muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
topic muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
description Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease’s severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.
publishDate 2021
dc.date.issued.fl_str_mv 2021
dc.date.accessioned.fl_str_mv 2023-07-25T20:17:28Z
dc.date.available.fl_str_mv 2023-07-25T20:17:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv ALONSO-PÉREZ, Jorge; GONZÁLEZ-QUEREDA, Lidia; BRUNO, Claudio; PANICUCCI, Chiara; ALAVI, Afagh; NAFISSI, Shahriar; NILIPOUR, Yalda; ZANOTELI, Edmar; ISIHI, Lucas Michielon de Augusto; MELEGH, Béla. Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy. Brain, [S.L.], v. 145, n. 2, p. 596-606, 13 set. 2021. Oxford University Press (OUP). http://dx.doi.org/10.1093/brain/awab301. Disponível em: https://academic.oup.com/brain/article/145/2/596/6369509?login=true. Acesso em: 13 jul. 2023.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/handle/123456789/54166
dc.identifier.doi.none.fl_str_mv http://dx.doi.org/10.1093/brain/awab301
identifier_str_mv ALONSO-PÉREZ, Jorge; GONZÁLEZ-QUEREDA, Lidia; BRUNO, Claudio; PANICUCCI, Chiara; ALAVI, Afagh; NAFISSI, Shahriar; NILIPOUR, Yalda; ZANOTELI, Edmar; ISIHI, Lucas Michielon de Augusto; MELEGH, Béla. Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy. Brain, [S.L.], v. 145, n. 2, p. 596-606, 13 set. 2021. Oxford University Press (OUP). http://dx.doi.org/10.1093/brain/awab301. Disponível em: https://academic.oup.com/brain/article/145/2/596/6369509?login=true. Acesso em: 13 jul. 2023.
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