Abstract：
We describe three patients with asymmetric congenital myopathy without definite nemaline bodies and one patient with severe nemaline myopathy. In all four patients, the phenotype had been caused by pathogenic missense variants in ACTA1 leading to the same amino acid change, p.(Gly247Arg). The three patients with milder myopathy were mosaic for their variants. In contrast, in the severely affected patient, the missense variant was present in a de novo, constitutional form. The grade of mosaicism in the three mosaic patients ranged between 20 % and 40 %. We speculate that the milder clinical and histological manifestations of the same ACTA1 variant in the patients with mosaicism reflect the lower abundance of mutant actin in their muscle tissue. Similarly, the asymmetry of body growth and muscle weakness may be a consequence of the affected cells being unevenly distributed. The partial improvement in muscle strength with age in patients with mosaicism might be due to an increased proportion over time of nuclei carrying and expressing two normal alleles.
摘要：
我们描述了三名没有明确线虫体的不对称先天性肌病患者和一名患有严重线虫肌病的患者。在所有四名患者中，该表型是由ACTA1中的致病性错义变体引起的，导致相同的氨基酸变化，p.（Gly247Arg）。三名患有轻度肌病的患者对其变体进行了马赛克。相比之下,在受影响严重的患者中，错觉变体存在于从头，宪法形式。三名马赛克患者的镶嵌性等级在20％至40％之间。我们推测，镶嵌性患者中相同ACTA1变体的较温和的临床和组织学表现反映了其肌肉组织中突变肌动蛋白的丰度较低。同样，身体生长和肌肉无力的不对称可能是受影响细胞分布不均匀的结果。镶嵌症患者随着年龄的增长，肌肉力量的部分改善可能是由于携带和表达两个正常等位基因的细胞核随着时间的推移比例增加。
