Perez F, Vital A, Martin-Negrier M-L, Ferrer X, Sole G
Département de neurologie, centre de référence des maladies neuromusculaires, groupe hospitalier Sud, CHU de Bordeaux, 33600 Pessac, France.
Rev Neurol (Paris). 2010 May;166(5):502-8. doi: 10.1016/j.neurol.2009.10.015. Epub 2009 Dec 30.
Limb girdle muscular dystrophies are rare genetic diseases. Despite constant progress in genetics and biochemistry, the pathogenic mechanisms are not completely understood. Calpainopathy (LGMD2A) has been reported to be the most frequent autosomal recessive form of muscular dystrophy in several populations. Point mutations in CAPN3 are difficult to identify and the analysis is long and costly. The use of western blot does not seem to provide the expected sensitivity and specificity.
We studied all the patients diagnosed in the neuromuscular center of Bordeaux (France) with confirmed calpainopathy in order to establish the appropriate diagnostic approach (inclusion criteria: muscular biopsy with calpain 3 western blot study, two mutations in CAPN3). Patients with highly suspected calpainopathy (same criteria with only one mutation) were also analyzed.
Our 13 patients belonged to 10 different families. Four patients had a normal western blot for calpain (WBn). We found high phenotypic variability with frequent atypical signs. The WBn group had less severe disease (a statistically significant later age of onset, a tendency toward lower CK levels and a slower disease course). We extended this comparison to the single mutation patients and we found the same results.
Considering the lack of sensitivity of western blot protein analysis in LGMD2A, a normal western blot for calpain should not halt the genetic analysis. The western blot result seems to have prognostic value. A normal western blot may help genetic testing by highlighting some mutational hot spots in the CAPN3 gene.
肢带型肌营养不良症是罕见的遗传性疾病。尽管遗传学和生物化学不断取得进展，但致病机制仍未完全明确。据报道，钙蛋白酶病（LGMD2A）是若干人群中最常见的常染色体隐性肌营养不良症形式。CAPN3中的点突变难以识别，分析过程漫长且成本高昂。蛋白质免疫印迹法似乎无法提供预期的敏感性和特异性。
我们研究了在法国波尔多神经肌肉中心确诊为钙蛋白酶病的所有患者，以确立适当的诊断方法（纳入标准：进行钙蛋白酶3蛋白质免疫印迹研究的肌肉活检，CAPN3中有两个突变）。对高度疑似钙蛋白酶病（相同标准但只有一个突变）的患者也进行了分析。
我们的13名患者分属10个不同家庭。4名患者的钙蛋白酶蛋白质免疫印迹结果正常（WBn）。我们发现表型变异性高，常有非典型体征。WBn组疾病较轻（发病年龄较晚，具有统计学意义，CK水平有降低趋势，病程进展较慢）。我们将这种比较扩展至单突变患者，结果相同。
鉴于蛋白质免疫印迹分析在LGMD2A中缺乏敏感性，钙蛋白酶蛋白质免疫印迹结果正常不应终止基因分析。蛋白质免疫印迹结果似乎具有预后价值。蛋白质免疫印迹结果正常可能通过突出CAPN3基因中的一些突变热点来帮助进行基因检测。
