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Portrait of Dysferlinopathy: Diagnosis and Development of Therapy

Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the DYSF gene. Dysferlin is a membrane protein in the sarcolemma and is involved in different functions, such as membrane repair and vesicle fusion, T-tubule development and maintenance, Ca(2+) signalling, and the regu...

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Autores principales: Bouchard, Camille, Tremblay, Jacques P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531777/
https://www.ncbi.nlm.nih.gov/pubmed/37762951
http://dx.doi.org/10.3390/jcm12186011
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author Bouchard, Camille
Tremblay, Jacques P.
author_facet Bouchard, Camille
Tremblay, Jacques P.
author_sort Bouchard, Camille
collection PubMed
description Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the DYSF gene. Dysferlin is a membrane protein in the sarcolemma and is involved in different functions, such as membrane repair and vesicle fusion, T-tubule development and maintenance, Ca(2+) signalling, and the regulation of various molecules. Miyoshi Myopathy type 1 (MMD1) and Limb–Girdle Muscular Dystrophy 2B/R2 (LGMD2B/LGMDR2) are two possible clinical presentations, yet the same mutations can cause both presentations in the same family. They are therefore grouped under the name dysferlinopathy. Onset is typically during the teenage years or young adulthood and is characterized by a loss of Achilles tendon reflexes and difficulty in standing on tiptoes or climbing stairs, followed by a slow progressive loss of strength in limb muscles. The MRI pattern of patient muscles and their biopsies show various fibre sizes, necrotic and regenerative fibres, and fat and connective tissue accumulation. Recent tools were developed for diagnosis and research, especially to evaluate the evolution of the patient condition and to prevent misdiagnosis caused by similarities with polymyositis and Charcot–Marie–Tooth disease. The specific characteristic of dysferlinopathy is dysferlin deficiency. Recently, mouse models with patient mutations were developed to study genetic approaches to treat dysferlinopathy. The research fields for dysferlinopathy therapy include symptomatic treatments, as well as antisense-mediated exon skipping, myoblast transplantation, and gene editing.
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spelling pubmed-105317772023-09-28 Portrait of Dysferlinopathy: Diagnosis and Development of Therapy Bouchard, Camille Tremblay, Jacques P. J Clin Med Review Dysferlinopathy is a disease caused by a dysferlin deficiency due to mutations in the DYSF gene. Dysferlin is a membrane protein in the sarcolemma and is involved in different functions, such as membrane repair and vesicle fusion, T-tubule development and maintenance, Ca(2+) signalling, and the regulation of various molecules. Miyoshi Myopathy type 1 (MMD1) and Limb–Girdle Muscular Dystrophy 2B/R2 (LGMD2B/LGMDR2) are two possible clinical presentations, yet the same mutations can cause both presentations in the same family. They are therefore grouped under the name dysferlinopathy. Onset is typically during the teenage years or young adulthood and is characterized by a loss of Achilles tendon reflexes and difficulty in standing on tiptoes or climbing stairs, followed by a slow progressive loss of strength in limb muscles. The MRI pattern of patient muscles and their biopsies show various fibre sizes, necrotic and regenerative fibres, and fat and connective tissue accumulation. Recent tools were developed for diagnosis and research, especially to evaluate the evolution of the patient condition and to prevent misdiagnosis caused by similarities with polymyositis and Charcot–Marie–Tooth disease. The specific characteristic of dysferlinopathy is dysferlin deficiency. Recently, mouse models with patient mutations were developed to study genetic approaches to treat dysferlinopathy. The research fields for dysferlinopathy therapy include symptomatic treatments, as well as antisense-mediated exon skipping, myoblast transplantation, and gene editing. MDPI 2023-09-16 /pmc/articles/PMC10531777/ /pubmed/37762951 http://dx.doi.org/10.3390/jcm12186011 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bouchard, Camille
Tremblay, Jacques P.
Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title_full Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title_fullStr Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title_full_unstemmed Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title_short Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
title_sort portrait of dysferlinopathy: diagnosis and development of therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531777/
https://www.ncbi.nlm.nih.gov/pubmed/37762951
http://dx.doi.org/10.3390/jcm12186011
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