Department of Neurology, Xiangya Hospital, Central South University, Xiangya Road, Kaifu District, Changsha, 410008, China.
Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, China.
Neurogenetics. 2022 Jan;23(1):37-44. doi: 10.1007/s10048-021-00681-2. Epub 2022 Jan 4.
Limb-girdle muscular dystrophy (LGMD) is a group of clinically and genetically heterogeneous neuromuscular disorders. LGMD-R7, which is caused by telethonin gene (TCAP) mutations, is one of the rarest forms of LGMD, and only a small number of LGMD-R7 cases have been described and mostly include patients from Brazil. A total of two LGMD-R7 patients were enrolled at a Chinese neuromuscular center. Demographic and clinical data were collected. Laboratory investigations and electromyography were performed. Routine and immunohistochemistry staining of muscle specimens was performed, and a next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders was used for analysis. The patients exhibited predominant muscle weakness. Electromyography revealed myopathic changes. The muscle biopsy showed myopathic features, such as increased fiber size variation, muscle fiber atrophy and regeneration, slight hyperplasia of the connective tissue, and disarray of the myofibrillar network. Two patients were confirmed to have mutations in the open reading frame of TCAP by next-generation sequencing. One patient had compound heterozygous mutations, and the other patient harbored a novel homozygous mutation. Western blotting analysis of the skeletal muscle lysate confirmed the absence of telethonin in the patients. We described two LGMD-R7 patients presenting a classical LGMD phenotype and a novel homozygous TCAP mutation. Our research expands the spectrum of LGMD-R7 due to TCAP mutations based on patients from a Chinese neuromuscular center.
肢带型肌营养不良症(LGMD)是一组具有临床和遗传异质性的神经肌肉疾病。由 telethonin 基因(TCAP)突变引起的 LGMD-R7 是 LGMD 中最罕见的形式之一,仅有少数 LGMD-R7 病例被描述,且大多来自巴西。我们在中国神经肌肉中心共纳入了 2 例 LGMD-R7 患者。收集了人口统计学和临床数据。进行了实验室检查和肌电图检查。对肌肉标本进行了常规和免疫组织化学染色,并使用与遗传性神经肌肉疾病相关的基因的下一代测序面板进行了分析。患者表现出明显的肌肉无力。肌电图显示肌病改变。肌肉活检显示肌病特征,如纤维大小变异增加、肌纤维萎缩和再生、结缔组织轻微增生以及肌原纤维网络排列紊乱。通过下一代测序,2 例患者证实存在 TCAP 开放阅读框的突变。1 例患者为复合杂合突变,另 1 例患者携带新的纯合突变。骨骼肌裂解物的 Western blot 分析证实患者中缺乏 telethonin。我们描述了 2 例具有经典 LGMD 表型和新型 TCAP 纯合突变的 LGMD-R7 患者。我们的研究基于来自中国神经肌肉中心的患者,扩展了由于 TCAP 突变导致的 LGMD-R7 的谱。