title: Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression.
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.
authors.affiliation: Neuromuscular Research Unit and Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. nanna.witting@regionh.dk
authors.forename: Nanna
authors.initials: N
authors.lastname: Witting
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.forename: Helle
authors.initials: H
authors.lastname: Petri
authors.forename: Thomas
authors.initials: T
authors.lastname: Krag
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.forename: Lars
authors.initials: L
authors.lastname: Kober
authors.forename: John
authors.initials: J
authors.lastname: Vissing
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000075368:Anoctamins; D001706:Biopsy; D015153:Blotting, Western; D009202:Cardiomyopathies / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D018118:Chloride Channels / Q000235:genetics* / Q000502:physiology; D015331:Cohort Studies; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis*; D053580:Muscle Strength / Q000502:physiology; D009136:Muscular Dystrophies / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: C547813:ANO5 protein, human; D000075368:Anoctamins; D018118:Chloride Channels; D009124:Muscle Proteins; D004247:DNA; D003402:Creatine Kinase