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

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...

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Principais autores: Dourado Junior, Mário Emílio Teixeira, Perez, Jorge Alonso, Quereda, Lidia Gonzalez, et, al
Outros Autores: https://orcid.org/0000-0002-9462-2294
Formato: article
Idioma:English
Publicado em: Brain
Assuntos:
muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
Endereço do item:https://repositorio.ufrn.br/handle/123456789/54166
http://dx.doi.org/10.1093/brain/awab301
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spelling ri-123456789-541662023-07-25T20:17:28Z Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy Dourado Junior, Mário Emílio Teixeira Perez, Jorge Alonso Quereda, Lidia Gonzalez et, al https://orcid.org/0000-0002-9462-2294 muscular dystrophies delta-sarcoglycan SGCD LGMD-R6/2F ( limb-girdle muscular dystrophies) 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. 2023-07-25T20:17:28Z 2023-07-25T20:17:28Z 2021 article 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. https://repositorio.ufrn.br/handle/123456789/54166 http://dx.doi.org/10.1093/brain/awab301 en Attribution 3.0 Brazil http://creativecommons.org/licenses/by/3.0/br/ application/pdf Brain
institution Repositório Institucional
collection RI - UFRN
language English
topic muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
spellingShingle muscular dystrophies
delta-sarcoglycan
SGCD
LGMD-R6/2F ( limb-girdle muscular dystrophies)
Dourado Junior, Mário Emílio Teixeira
Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
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.
author2 https://orcid.org/0000-0002-9462-2294
author_facet https://orcid.org/0000-0002-9462-2294
Dourado Junior, Mário Emílio Teixeira
Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
format article
author Dourado Junior, Mário Emílio Teixeira
Perez, Jorge Alonso
Quereda, Lidia Gonzalez
et, al
author_sort Dourado Junior, Mário Emílio Teixeira
title Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy
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
publisher Brain
publishDate 2023
url https://repositorio.ufrn.br/handle/123456789/54166
http://dx.doi.org/10.1093/brain/awab301
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AT queredalidiagonzalez clinicalandgeneticspectrumofalargecohortofpatientswithdsarcoglycanmusculardystrophy
AT etal clinicalandgeneticspectrumofalargecohortofpatientswithdsarcoglycanmusculardystrophy
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