Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5
Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANO5
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DOI：
10.1212/wnl.0b013e31824c4682
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发表时间：
2012-03-01
期刊：
影响因子：
9.9
通讯作者：
Udd, B.
中科院分区：
文献类型：
--
作者：
Penttila, S.;Palmio, J.;Udd, B.
目的：描述了8种新的ANO 5突变，并显著扩展了与先前已知和未知突变相关的临床表型谱，以提高诊断准确性。在我们位于芬兰的四级转诊中心，95名患者中的101名患者的DNA样本，这些患者患有未确定的肢带型肌营养不良症（LGMD）、小腿远端肌病或肌酸激酶（CK）升高超过2,000 IU/L，结果：25例肌营养不良症患者均为ANO 5基因的11种不同隐性突变所致，ANO 5基因的突变频率为100 ~ 1000 bp。绝大多数突变，11个中的8个，被证明是以前未知的新突变。最常见的突变，c.2272C>T（p.R758C），出现在20例患者。与此相关的表型和常见的欧洲突变，c.191dupA，变化从几乎无症状的高高CK血症严重LGMD与一贯温和的表型在女性patients.Conclusions：突变在ANO 5是一个常见的原因不明的肌营养不良症，与远端和近端介绍。其他类型包括高CK血症、肌痛或小腿肥大，数十年无明显虚弱，尤其是女性患者。突变分布在整个基因中，表明由ANO 5引起的肌营养不良症预计会在所有人群中发生。神经病学（R）2012;78：897-903
Objective: Description of 8 new ANO5 mutations and significant expansion of the clinical phenotype spectrum associated with previously known and unknown mutations to improve diagnostic accuracy.Methods: DNA samples of 101 patients in 95 kindreds at our quaternary referral center in Finland, who had undetermined limb-girdle muscular dystrophy (LGMD), calf distal myopathy, or creatine kinase (CK) elevations of more than 2,000 IU/L, were selected for ANO5 genetic evaluation, and the clinical findings of patients with mutations were retrospectively analyzed.Results: A total of 25 patients with muscular dystrophy caused by 11 different recessive mutations in the ANO5 gene were identified. The vast majority of mutations, 8 of 11, proved to be previously unknown new mutations. The most frequent mutation, c.2272C>T (p.R758C), was present in 20 patients. The phenotypes associated with this and the common European mutation, c.191dupA, varied from nearly asymptomatic high hyperCKemia to severe LGMD with consistently milder phenotypes in female patients.Conclusions: Mutations in ANO5 are a frequent cause of undetermined muscular dystrophy, with both distal and proximal presentation. Other types include high hyperCKemia, myalgia, or calf hypertrophy over decades without significant weakness, especially in female patients. Mutations are distributed all over the gene, indicating that muscular dystrophy caused by ANO5 can be expected to occur in all populations. Neurology (R) 2012;78:897-903