Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE.
Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations in PLEC1 and CHRNE.
复制标题
与 PLEC1 和 CHRNE 纯合突变引起的大疱性表皮松解症相关的先天性肌无力综合征。
DOI：
10.1111/j.1399-0004.2010.01602.x
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发表时间：
2011
影响因子：
3.5
通讯作者：
Wollmann,RL
中科院分区：
文献类型：
--
作者：
Maselli,RA;Arredondo,J;Cagney,O;Mozaffar,T;Skinner,S;Yousif,S;Davis,RR;Gregg,JP;Sivak,M;Konia,TH;Thomas,K;Wollmann,RL
Maselli RA、Arredondo J、Cagney O、Mozaffar T、Skinner S、Yousif S、Davis RR、Gregg JP、Sivak M、Konia TH、Thomas K、Wollmann RL。由PLEC1和CHRNE纯合突变引起的与大疱性表皮松解症相关的先天性肌无力综合征。凝集素基因（PLEC1）突变导致单纯性大疱性表皮松解症（EBS），这可能与肌营养不良症（EBS-MD）或幽门闭锁（EBS-PA）有关。 EBS 与先天性肌无力综合征 (CMS) 的关联也被怀疑是由 PLEC1 突变引起的。我们在这里报道了一名患有 EBS 和 CMS 的近亲患者，其 PLEC1 突变分析显示纯合 36 个核苷酸插入 (1506_1507ins36)，导致患者肌肉中 PLEC1mRNA 和凝集素的表达减少。此外，CHRNE 的突变分析揭示了 1293insG 的纯合子，这是一种众所周知的低表达受体突变。皮肤活检显示 EBS 迹象，肘肌活检显示轻度肌病迹象。终板研究显示终板碎片、突触后简化和大量线状线粒体。微型终板电位的幅度减小了，但终板量子含量实际上增加了。这里呈现的复杂表型是由两个独立基因的突变造成的。虽然皮肤表现是由于 PLEC1 突变所致，但患者的神经肌肉接头处存在 PLEC1 和 CHRNE 突变足迹，表明这两个基因的异常导致了 CMS 表型。
Maselli RA, Arredondo J, Cagney O, Mozaffar T, Skinner S, Yousif S, Davis RR, Gregg JP, Sivak M, Konia TH, Thomas K, Wollmann RL. Congenital myasthenic syndrome associated with epidermolysis bullosa caused by homozygous mutations inPLEC1andCHRNE.Mutations in the plectin gene (PLEC1)cause epidermolysis bullosa simplex (EBS), which may associate with muscular dystrophy (EBS–MD) or pyloric atresia (EBS–PA). The association of EBS with congenital myasthenic syndrome (CMS) is also suspected to result fromPLEC1mutations. We report here a consanguineous patient with EBS and CMS for whom mutational analysis ofPLEC1revealed a homozygous 36 nucleotide insertion(1506_1507ins36)that results in a reduced expression ofPLEC1mRNA and plectin in the patient muscle. In addition, mutational analysis ofCHRNErevealed a homozygous1293insG, which is a well‐known low‐expressor receptor mutation. A skin biopsy revealed signs of EBS, and an anconeus muscle biopsy showed signs of a mild myopathy. Endplate studies showed fragmentation of endplates, postsynaptic simplification, and large collections of thread‐like mitochondria. Amplitudes of miniature endplate potentials were diminished, but the endplate quantal content was actually increased. The complex phenotype presented here results from mutations in two separate genes. While the skin manifestations are because of thePLEC1mutation, footprints of mutations inPLEC1andCHRNEare present at the neuromuscular junction of the patient indicating that abnormalities in both genes contribute to the CMS phenotype.