ACTA1 gene encodes the skeletal muscle alpha-actin, the core of thin filaments of the sarcomere. ACTA1 mutations are responsible of several muscle disorders including nemaline, cores, actin aggregate myopathies and fiber-type disproportion. We report clinical, muscle imaging, histopatological and genetic data of an Italian family carrying a novel ACTA1 mutation. All affected members showed a late-presenting, diffuse muscle weakness with sternocleidomastoideus and temporalis atrophy. Mild dysmorphic features were also detected. The most affected muscles by muscle MRI were rectus abdominis, gluteus minimus, vastus intermedius and both gastrocnemii. Muscle biopsy showed the presence of nemaline bodies with several unusual dark areas at Gomori Trichrome, corresponding to unstructured cores with abundant electrodense material by electron microscopy. The molecular analysis revealed missense variant c.148G>A; p.(Gly50Ser) in the exon 3 of ACTA1, segregating with affected members in the family. We performed a functional essay of fibre contractility showing a higher pCa50 (a measure of the calcium sensitivity of force) of type 1 fibers compared to control subjects' type 1 muscle fibers. Our findings expand the clinico-pathological spectrum of ACTA1-related congenital myopathies and the genetic spectrum of core-rod myopathies.

中文翻译：

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新的 ACTA1 突变导致具有不寻常暗核的晚期线状体肌病

ACTA1 基因编码骨骼肌α-肌动蛋白，肌节细丝的核心。ACTA1 突变是导致多种肌肉疾病的原因，包括线状体、核心、肌动蛋白聚集性肌病和纤维类型不成比例。我们报告了一个携带新型 ACTA1 突变的意大利家庭的临床、肌肉成像、组织病理学和遗传数据。所有受影响的成员都表现出迟发性、弥漫性肌肉无力，伴有胸锁乳突肌和颞肌萎缩。还检测到轻度畸形特征。肌肉 MRI 影响最大的肌肉是腹直肌、臀小肌、股中间肌和腓肠肌。肌肉活检显示在 Gomori Trichrome 处存在具有数个不寻常暗区的线状体，对应于电子显微镜下具有丰富电密度材料的非结构化核心。分子分析显示错义变异c.148G>A；p.(Gly50Ser) 在 ACTA1 的外显子 3 中，与受影响的家庭成员隔离。我们进行了一项关于纤维收缩性的功能性论文，显示与对照受试者的 1 型肌纤维相比，1 型纤维具有更高的 pCa50（力的钙敏感性的量度）。我们的研究结果扩展了 ACTA1 相关先天性肌病的临床病理谱和核心杆肌病的遗传谱。