PDF(Pubmed)
Abstract：
UNASSIGNED: Congenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a fatal outcome in the most severe cases but can either be benign or lead to an amelioration even in severe presentations. Muscle biopsy analysis is crucial for the identification of pathognomonic morphological features, such as core areas, nemaline bodies or rods, nuclear centralizations and congenital type 1 fibers disproportion. However, multiple abnormalities in the same muscle can be observed, making more complex the myopathological scenario.
UNASSIGNED: Here, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.
UNASSIGNED: Our case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations.
UNASSIGNED: Here, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.
UNASSIGNED: Our case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations.
摘要：
■先天性肌病是一组异质性遗传性疾病，主要表现为早发性肌张力减退和肌无力。临床表型谱可以是高度可变的，从非常温和到严重的演讲。该过程也有很大差异，导致在最严重的情况下致命的结果，但可以是良性的或导致改善，即使在严重的表现。肌肉活检分析对于识别病理形态学特征至关重要，如核心领域，线虫体或杆，核集中化和先天性1型纤维不均衡。然而,可以观察到同一肌肉中的多个异常，使肌肉病理情况变得更加复杂。
■这里，我们描述了一个意大利新生儿出现严重的低张力症，呼吸功能不全,无法吸吮和吞咽，需要机械通气和胃造口术喂养。通过光学显微镜分析的肌肉活检显示存在充满糖原的空泡，提示代谢性肌病，但也有嗜血的夹杂物。超微结构研究证实了正常结构糖原的存在，以及微型棒的存在，将诊断假设引导到线虫肌病。针对先天性肌病基因的扩展的下一代测序分析揭示了ACTA1基因中存在新的杂合c.965T>Ap。（Leu322Gln）变体，编码骨骼肌α-肌动蛋白。
■我们的案例扩展了在活动病中观察到的分子和病理特征。我们强调了超微结构检查的价值，以调查在组织学水平上检测到的异常。我们还强调了在神经肌肉患者的分子分析中使用扩展的基因面板，特别是对于那些出现多重活检改变的人。
■这里，我们描述了一个意大利新生儿出现严重的低张力症，呼吸功能不全,无法吸吮和吞咽，需要机械通气和胃造口术喂养。通过光学显微镜分析的肌肉活检显示存在充满糖原的空泡，提示代谢性肌病，但也有嗜血的夹杂物。超微结构研究证实了正常结构糖原的存在，以及微型棒的存在，将诊断假设引导到线虫肌病。针对先天性肌病基因的扩展的下一代测序分析揭示了ACTA1基因中存在新的杂合c.965T>Ap。（Leu322Gln）变体，编码骨骼肌α-肌动蛋白。
■我们的案例扩展了在活动病中观察到的分子和病理特征。我们强调了超微结构检查的价值，以调查在组织学水平上检测到的异常。我们还强调了在神经肌肉患者的分子分析中使用扩展的基因面板，特别是对于那些出现多重活检改变的人。
