PDF(Pubmed)
Abstract：
Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.
摘要：
肌营养不良蛋白病是由DMD的致病变异引起的肌肉疾病，人类中描述的最大的基因，代表一系列疾病，从无症状的肌酸磷酸激酶升高到严重的杜氏肌营养不良（DMD）。目前正在使用或正在开发几种治疗策略，每个针对不同的致病变体。然而,对巴西东北部肌营养不良症患者的遗传特征知之甚少。我们描述了巴西东北部单个中心的致病性DMD变体谱。这是一个观察,采用多重连接依赖性探针扩增(MLPA)和基于下一代测序(NGS)的策略,对诊断为肌营养不良蛋白病的男性患者进行分子遗传学分析,进行横断面研究.总共对94例男性患者进行了评估。缺失（43.6％）和重复（10.6％）是致病变异的最常见模式。然而,47.1%的患者存在小变异，其中大多数是无意义变体(27.6%)。这是迄今为止最大的南美单中心肌萎缩蛋白病病例系列。我们发现与大多数先前的研究相比，可治疗的无义单核苷酸变体的频率更高。这些发现可能会对鲜为人知的人群的诊断策略产生影响，作为更高的频率的无义变异可能意味着更高的可能性治疗患者的疾病改善药物.
