Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , |
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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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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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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. |
url |
https://repositorio.ufrn.br/handle/123456789/54166 http://dx.doi.org/10.1093/brain/awab301 |
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