Ozyilmaz Berk, Kirbiyik Ozgur, Ozdemir Taha R, Ozer Ozge Kaya, Kutbay Yasar B, Erdogan Kadri M, Guvenc Merve Saka, Arıkan Şener, Turk Tuba Sozen, Kale Murat Yıldırım, Uludag Irem Fatma, Baydan Figen, Sertpoyraz Filiz, Gencpinar Pinar, Diniz Gulden
Genetic Diagnosis Center, Tepecik Training and Research Hospital, University of Health Sciences, Bornova Building, Sanayi Caddesi No 7, Bornova, Izmir, Turkey.
Department of Neurology, Tepecik Training and Research Hospital, University of Health Sciences, Izmir, Turkey.
Neurogenetics. 2022 Apr;23(2):103-114. doi: 10.1007/s10048-022-00687-4. Epub 2022 Feb 14.
Calpainopathy is mainly characterized by symmetric and progressive weakness of proximal muscles. Several reports showed that the most common LGMD subtype is LGMDR1 or calpainopathy, which had previously been defined as LGMD2A. Until now, more than 500 likely pathogenic/pathogenic variants in the CAPN3 gene have been reported. However, a clear genotype-phenotype association had not yet been established and this causes major difficulties in predicting the prognosis in asymptomatic patients and in providing genetic counseling for prenatal diagnosis. In this report, we aimed to add new data to the literature by evaluating 37 patients with likely pathogenic/pathogenic variants for the detected variants' nature, patients' phenotypes, and histopathological features. As a result, the general clinical presentation of the 23 different variants was presented, the high frequency of NM_000070.3:c.550delA mutation in Exon 4 was discussed, and some novel genotype-phenotype associations were suggested. We have underlined that calpainopathy can be misdiagnosed with inflammatory myopathies histopathologically. We have also emphasized that, in young or adult patients with mild to moderate proximal muscle weakness and elevated CK levels, calpainopathy should be the first suspected diagnosis.
钙蛋白酶病主要特征为近端肌肉对称性进行性无力。多项报告显示，最常见的肢带型肌营养不良（LGMD）亚型是LGMDR1或钙蛋白酶病，此前被定义为LGMD2A。截至目前，已报告了CAPN3基因中500多个可能致病/致病的变异。然而，尚未建立明确的基因型-表型关联，这给预测无症状患者的预后以及为产前诊断提供遗传咨询带来了重大困难。在本报告中，我们旨在通过评估37例携带可能致病/致病变异的患者的检测变异性质、患者表型和组织病理学特征，为文献增添新数据。结果，展示了23种不同变异的一般临床表现，讨论了外显子4中NM_000070.3:c.550delA突变的高频率，并提出了一些新的基因型-表型关联。我们强调，在组织病理学上，钙蛋白酶病可能会被误诊为炎症性肌病。我们还强调，对于轻度至中度近端肌肉无力且肌酸激酶（CK）水平升高的年轻或成年患者，钙蛋白酶病应是首先怀疑的诊断。
