Dysferlinopathy in Tunisia: clinical spectrum, genetic background and prognostic profile.

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  • Additional Information
    • Source:
      Publisher: Pergamon Press Country of Publication: England NLM ID: 9111470 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2364 (Electronic) Linking ISSN: 09608966 NLM ISO Abbreviation: Neuromuscul Disord Subsets: MEDLINE
    • Publication Information:
      Original Publication: Oxford ; New York : Pergamon Press, c1991-
    • Subject Terms:
      Muscular Dystrophies, Limb-Girdle*/genetics ; Muscular Dystrophies, Limb-Girdle*/metabolism ; Distal Myopathies*/genetics; Humans ; Middle Aged ; Prognosis ; Tunisia/epidemiology ; Membrane Proteins/genetics ; Muscle Proteins/genetics ; Dysferlin/genetics ; Disease Progression ; Mutation ; Genetic Background
    • Abstract:
      Dysferlinopathy is a rare group of hereditary muscular dystrophy with an autosomal recessive mode of inheritance caused by a mutation in the DYSF gene. It encodes for the dysferlin protein, which has a crucial role in multiple cellular processes, including muscle fiber membrane repair. This deficit has heterogeneous clinical presentations. In this study, we collected 20 Tunisian patients with a sex ratio of 1 and a median age of 50.5 years old (Interquartile range (IQR) = [36,5-54,75]). They were followed for periods ranging from 5 to 48 years. The median age at onset was 17 years old (IQR = [16,8-28,4]). Five major phenotypes were identified: Limb-girdle muscular dystrophy (LGMDR2) (35%), a proximodistal phenotype (35%), Miyoshi myopathy (10%),  Distal myopathy with anterior tibial onset (DMAT) (10%), and asymptomatic HyperCKemia (10%). At the last evaluation, more than half of patients (55%) were on wheelchair. Loss of ambulation occurred generally during the fourth decade. After 20 years of disease progression, two patients with a proximodistal phenotype (10%) developed dilated cardiomyopathy and mitral valve regurgitation. Restrictive respiratory syndrome was observed in three patients (DMAT: 1 patient, proximodistal phenotype: 1 patient, LGMDR2: 1 patient). Genetic study disclosed five mutations. We observed clinical heterogeneity between families and even within the same family. Disease progression was mainly slow to intermediate regardless of the phenotype.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2023. Published by Elsevier B.V.)
    • Contributed Indexing:
      Keywords: Distal myopathy; Dysferlin protein; Limb girdle muscular dystrophy type 2; Miyoshi myopathy; Tunisia
    • Accession Number:
      0 (Membrane Proteins)
      0 (Muscle Proteins)
      0 (Dysferlin)
    • Subject Terms:
      Dysferlinopathy; Limb-girdle muscular dystrophy, type 2B; Myopathy, Distal, with Anterior Tibial Onset
    • Publication Date:
      Date Created: 20230916 Date Completed: 20231106 Latest Revision: 20231106
    • Publication Date:
      20250114
    • Accession Number:
      10.1016/j.nmd.2023.08.007
    • Accession Number:
      37716854