Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.
Cytoplasmic body pathology in severe ACTA1-related myopathy in the absence of typical nemaline rods.
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DOI：
10.1016/j.nmd.2017.02.012
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Bönnemann CG
中科院分区：
文献类型：
--
作者：
Donkervoort S;Chan SHS;Hayes LH;Bradley N;Nguyen D;Leach ME;Mohassel P;Hu Y;Thangarajh M;Bharucha-Goebel D;Kan A;Ho RSL;Reyes CA;Nance J;Moore SA;Foley AR;Bönnemann CG
ACTA 1突变导致一组具有扩大的临床和组织病理学异质性的肌病。我们描述了3例严重ACTA 1相关肌病患者，他们有肌纤维胞质体，但没有经典的杆状体。患者1是一名5岁男孩，出生时出现严重虚弱和呼吸衰竭，需要机械通气。全外显子组测序鉴定了杂合c.282C>A（p.Asn94Lys）ACTA 1突变。患者2和3是双胞胎男孩，出生时张力减退、严重虚弱和呼吸功能不全，需要机械通气。两人都在6个月大时死亡。通过全外显子组测序鉴定了相同的杂合c.282C>A（p.Asn94Lys）ACTA 1突变。我们的结论是，临床上严重的ACTA 1相关性肌病可以提出与肌肉形态学的结果，提示细胞质体肌病在没有明确的线状杆。骨骼肌肌节α-肌动蛋白中的Asn 94 Lys突变可能与这种组织学表现有关。这些新的ACTA 1病例也说明了全外显子组测序在直接获得具有已知神经肌肉基因的意外表型和组织学特征的患者的候选遗传诊断中的成功应用。
Mutations in ACTA1 cause a group of myopathies with expanding clinical and histopathological heterogeneity. We describe three patients with severe ACTA1-related myopathy who have muscle fiber cytoplasmic bodies but no classic nemaline rods. Patient 1 is a five-year-old boy who presented at birth with severe weakness and respiratory failure, requiring mechanical ventilation. Whole exome sequencing identified a heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation. Patients 2 and 3 were twin boys with hypotonia, severe weakness, and respiratory insufficiency at birth requiring mechanical ventilation. Both died at 6 months of age. The same heterozygous c.282C>A (p.Asn94Lys) ACTA1 mutation was identified by whole exome sequencing. We conclude that clinically severe ACTA1-related myopathy can present with muscle morphological findings suggestive of cytoplasmic body myopathy in the absence of definite nemaline rods. The Asn94Lys mutation in skeletal muscle sarcomeric α-actin may be linked to this histological appearance. These novel ACTA1 cases also illustrate the successful application of whole exome sequencing in directly arriving at a candidate genetic diagnosis in patients with unexpected phenotypic and histologic features for a known neuromuscular gene.
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影响因子：
1.9
作者：
Ladha, Shafeeq;Coons, Stephen;Sivakumar, Kumaraswamy
通讯作者：
Sivakumar, Kumaraswamy
影响因子：
9.9
作者：
Ryan, MM;Ilkovski, B;Beggs, AH
通讯作者：
Beggs, AH
影响因子：
1.4
作者：
GOEBEL, HH;SCHLOON, H;LENARD, HG
通讯作者：
LENARD, HG
DOI：
10.1212/nxg.0000000000000019
发表时间：
2015-08
期刊：
Neurology. Genetics
影响因子：
--
作者：
Foley AR;Donkervoort S;Bönnemann CG
通讯作者：
Bönnemann CG
影响因子：
3.4
作者：
Kaimaktchiev, Vassil;Goebel, Hans;Nixon, Randal
通讯作者：
Nixon, Randal