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Abstract：
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：神经肌病，最常见的先天性肌病，是由各种基因突变引起的.在这项研究中,我们试图调查临床特征，15例线虫性肌病患者的肌肉病理和遗传特征。
结果：在15名患者中，男性9例(60.00%),女性6例(40.00%),其中9人(60.00%)分别来自三个家庭。看病的年龄从9岁到52岁不等,发病年龄从5岁到23岁，病程3～35年。15名患者中有10名具有高拱形腭和拉长的面部。只有一名患者有轻度呼吸肌受累，没有一名患者有吞咽困难。15例患者中有9例进行了肌肉活检。病理上,不同大小的肌肉纤维，可以发现萎缩性肌纤维和代偿性肥大纤维，偶尔观察到变性和坏死的肌纤维。在所有9例患者中都可以看到不同程度的线虫体聚集。NEB基因惹起的线虫性肌病患者Ⅰ型和Ⅱ型肌纤维散布显著异常，然而,TPM3基因和ACTA1基因引起的线虫性肌病患者基本正常。6例患者的电镜分析显示,5例(83.33%)患者发现肌原纤维间聚集的线虫体,大部分位于Z波段附近,但没有发现核内棒.对15例NM患者进行基因分析,发现携带3个NM相关基因,包括11例（73.33%）NEB患者，TPM3患者3例（20.00%），ACTA1患者1例（6.67%）。共鉴定出12个突变位点,包括10个(83.33%)外显子突变和2个(16.67%)内含子突变。
结论：线虫性肌病的临床表型高度异质性。肌肉病理学显示，线虫体聚集是诊断NM的重要特征。NEB是该队列中最常见的致病基因。剪接突变，c.21522+3A>G可能是中国NEB基因的热点突变。
结果：在15名患者中，男性9例(60.00%),女性6例(40.00%),其中9人(60.00%)分别来自三个家庭。看病的年龄从9岁到52岁不等,发病年龄从5岁到23岁，病程3～35年。15名患者中有10名具有高拱形腭和拉长的面部。只有一名患者有轻度呼吸肌受累，没有一名患者有吞咽困难。15例患者中有9例进行了肌肉活检。病理上,不同大小的肌肉纤维，可以发现萎缩性肌纤维和代偿性肥大纤维，偶尔观察到变性和坏死的肌纤维。在所有9例患者中都可以看到不同程度的线虫体聚集。NEB基因惹起的线虫性肌病患者Ⅰ型和Ⅱ型肌纤维散布显著异常，然而,TPM3基因和ACTA1基因引起的线虫性肌病患者基本正常。6例患者的电镜分析显示,5例(83.33%)患者发现肌原纤维间聚集的线虫体,大部分位于Z波段附近,但没有发现核内棒.对15例NM患者进行基因分析,发现携带3个NM相关基因,包括11例（73.33%）NEB患者，TPM3患者3例（20.00%），ACTA1患者1例（6.67%）。共鉴定出12个突变位点,包括10个(83.33%)外显子突变和2个(16.67%)内含子突变。
结论：线虫性肌病的临床表型高度异质性。肌肉病理学显示，线虫体聚集是诊断NM的重要特征。NEB是该队列中最常见的致病基因。剪接突变，c.21522+3A>G可能是中国NEB基因的热点突变。
