Department of Neurology, Jiaozuo People's Hospital of Henan Province, Henan, 454002, Henan Province, People's Republic of China.
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
Acta Neurol Belg. 2024 Feb;124(1):91-99. doi: 10.1007/s13760-023-02333-8. Epub 2023 Jul 31.
Nemaline myopathy, the most common of the congenital myopathies, is caused by various genetic mutations. In this study, we attempted to investigate the clinical features, muscle pathology and genetic features of 15 patients with nemaline myopathy.
Among the 15 patients, there were 9 (60.00%) males and 6 (40.00%) females, and 9 (60.00%) of them came from three families respectively. The age of seeing a doctor ranged from 9 to 52 years old, the age of onset was from 5 to 23 years old, and the duration of disease ranged from 3 to 35 years. Ten out of the 15 patients had high arched palate and elongated face. Only one patient had mild respiratory muscle involvement and none had dysphagia. Muscle biopsies were performed in 9 out of the 15 patients. Pathologically, muscle fibers of different sizes, atrophic muscle fibers and compensatory hypertrophic fibers could be found, and occasionally degenerated and necrotic muscle fibers were observed. Different degrees of nemaline bodies aggregation could be seen in all 9 patients. The distribution of type I and type II muscle fibers were significantly abnormal in patients with nemaline myopathy caused by NEB gene, however, it was basically normal in patients with nemaline myopathy caused by TPM3 gene and ACTA1 gene. Electron microscopic analysis of 6 patients showed that nemaline bodies aggregated between myofibrils were found in 5(83.33%) cases, and most of them were located near the Z band, but no intranuclear rods were found. The gene analysis of 15 NM patients showed that three NM-related genes were harbored, including 11 (73.33%) patients with NEB, 3 (20.00%) patients with TPM3, and 1 (6.67%) patient with ACTA1, respectively. A total of 12 mutation sites were identified and included 10 (83.33%) mutations in exon and 2(16.67%) mutations in intron.
The clinical phenotype of nemaline myopathy is highly heterogeneous. Muscle pathology shows that nemaline bodies aggregation is an important feature for the diagnosis of NM. NEB is the most frequent causative gene in this cohort. The splicing mutation, c.21522 + 3A > G may be the hotspot mutation of the NEB gene in Chinese NM patients.
先天性肌病中最常见的是肌强直性营养不良，由各种基因突变引起。在这项研究中，我们试图研究 15 例肌强直性营养不良患者的临床特征、肌肉病理学和遗传特征。
在 15 例患者中，有 9 例（60.00%）为男性，6 例（40.00%）为女性，其中 9 例（60.00%）分别来自 3 个家庭。就诊年龄为 9-52 岁，发病年龄为 5-23 岁，病程为 3-35 年。15 例患者中有 10 例存在高拱形腭和长脸。只有 1 例患者有轻微的呼吸肌受累，无吞咽困难。在 15 例患者中有 9 例行肌肉活检。病理上可发现不同大小的肌纤维、萎缩肌纤维和代偿性肥大纤维，偶尔可观察到退行性和坏死性肌纤维。所有 9 例患者均可见不同程度的杆状体聚集。由 NEB 基因引起的肌强直性营养不良患者的 I 型和 II 型肌纤维分布明显异常，但由 TPM3 基因和 ACTA1 基因引起的肌强直性营养不良患者基本正常。对 6 例患者的电镜分析显示，5 例（83.33%）患者肌原纤维之间存在杆状聚集，大多数位于 Z 带附近，但未发现核内棒。15 例 NM 患者的基因分析显示，共携带 3 个 NM 相关基因，其中 11 例（73.33%）为 NEB 基因，3 例（20.00%）为 TPM3 基因，1 例（6.67%）为 ACTA1 基因。共发现 12 个突变位点，包括 10 个（83.33%）exon 突变和 2 个（16.67%）intron 突变。
肌强直性营养不良的临床表型高度异质。肌肉病理学显示，杆状聚集是 NM 诊断的重要特征。NEB 是本队列中最常见的致病基因。剪接突变 c.21522+3A>G 可能是中国 NM 患者中 NEB 基因的热点突变。
