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Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression

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Abstract

Since the initial description in 2010 of anoctamin 5 deficiency as a cause of muscular dystrophy, a handful of papers have described this disease in cases of mixed populations. We report the first large regional study and present data on new aspects of prevalence, muscular and cardiac phenotypic characteristics, and muscle protein expression. All patients in our neuromuscular unit with genetically unclassified, recessive limb girdle muscular dystrophy (LGMD2), Miyoshi-type distal myopathy (MMD) or persistent asymptomatic hyperCK-emia (PACK) were assessed for mutations in the ANO5 gene. Genetically confirmed patients were evaluated with muscular and cardiopulmonary examination. Among 40 unclassified patients (28 LGMD2, 5 MMD, 7 PACK), 20 were homozygous or compound heterozygous for ANO5 mutations, (13 LGMD2, 5 MMD, 2 PACK). Prevalence of ANO5 deficiency in Denmark was estimated at 1:100.000 and ANO5 mutations caused 11 % of our total cohort of LGMD2 cases making it the second most common LGMD2 etiology in Denmark. Eight patients complained of dysphagia and 3 dated symptoms of onset in childhood. Cardiac examinations revealed increased frequency of premature ventricular contractions. Four novel putative pathogenic mutations were discovered. Total prevalence and distribution of phenotypes of ANO5 disease in a representative regional cohort are described for the first time. A high prevalence of ANO5 deficiency was found among patients with unclassified LGMD2 (46 %) and MMD (100 %). The high incidence of reported dysphagia is a new phenotypic feature not previously reported, and cardiac investigations revealed that ANO5-patients may have an increased risk of ventricular arrhythmia.

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Conflicts of interest

Dr. Vissing has received research support, honoraria, and travel funding from the Genzyme Corporation, and is a member of the Global Advisory Board for Pompe Disease for Genzyme Corporation. Dr. Vissing has also worked as a consultant/advisor for Lundbeck Pharmaceutical Company, and as a drug safety consultant for Cardoz AB, Sweden.

Ethical standard

The patients were fully informed and agreed to participate and to publication of the results. The study was carried out according to the ethical standards laid down by the Helsinki declaration in 1964 and further on.

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Authors and Affiliations

  1. Neuromuscular Research Unit and Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Nanna Witting, Thomas Krag & John Vissing

  2. Department of Clinical Genetics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Morten Duno

  3. The Unit for Inherited Cardiac Diseases, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    Helle Petri, Henning Bundgaard & Lars Kober

Authors
  1. Nanna Witting
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  2. Morten Duno
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  3. Helle Petri
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  4. Thomas Krag
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  5. Henning Bundgaard
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  6. Lars Kober
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  7. John Vissing
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Correspondence to Nanna Witting.

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Witting, N., Duno, M., Petri, H. et al. Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression. J Neurol 260, 2084–2093 (2013). https://doi.org/10.1007/s00415-013-6934-y

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  • DOI: https://doi.org/10.1007/s00415-013-6934-y

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