Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression
Anoctamin 5 muscular dystrophy in Denmark: prevalence, genotypes, phenotypes, cardiac findings, and muscle protein expression
复制标题
DOI：
10.1007/s00415-013-6934-y
复制
发表时间：
2013-05
影响因子：
6
通讯作者：
N. Witting;M. Duno;Helle Petri;T. Krag;H. Bundgaard;L. Køber;J. Vissing
中科院分区：
文献类型：
--
作者：
N. Witting;M. Duno;Helle Petri;T. Krag;H. Bundgaard;L. Køber;J. Vissing
自2010年首次描述anoctamin 5缺乏症是肌营养不良症的原因以来，少数论文在混合人群中描述了这种疾病。我们报告了第一个大的区域性研究，并提供了关于患病率、肌肉和心脏表型特征以及肌肉蛋白表达的新方面的数据。我们的神经肌肉科所有患有遗传学未分类的隐性肢带型肌营养不良症（LGMD 2）、三好型远端肌病（MMD）或持续无症状高CK血症（PACK）的患者均进行了ANO 5基因突变的评估。通过肌肉和心肺检查对遗传学确诊的患者进行评价。在40例未分类的患者中（LGMD 2 28例，MMD 5例，PACK 7例），20例为ANO 5突变纯合子或复合杂合子（LGMD 2 13例，MMD 5例，PACK 2例）。在丹麦，ANO 5缺陷的患病率估计为1：100.000，ANO 5突变导致我们的LGMD 2病例总队列的11%，使其成为丹麦第二常见的LGMD 2病因。8例患者主诉吞咽困难，3例在儿童期发病。心脏检查显示室性早搏频率增加。发现了四种新的推定致病突变。首次描述了代表性区域队列中ANO 5疾病表型的总患病率和分布。在未分类的LGMD 2（46%）和MMD（100%）患者中发现ANO 5缺乏症的高患病率。报告的吞咽困难的高发生率是以前未报告的新表型特征，心脏检查显示ANO 5-患者可能具有增加的室性心律失常风险。
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 theANO5gene. 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 forANO5mutations, (13 LGMD2, 5 MMD, 2 PACK). Prevalence of ANO5 deficiency in Denmark was estimated at 1:100.000 andANO5mutations 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.