Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings
Plastin 3 expression in discordant spinal muscular atrophy (SMA) siblings
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DOI：
10.1016/j.nmd.2011.03.009
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发表时间：
2011-06-01
影响因子：
2.8
通讯作者：
Tizzano, Eduardo F.
中科院分区：
文献类型：
--
作者：
Bernal, Sara;Also-Rallo, Eva;Tizzano, Eduardo F.
脊髓性肌萎缩症(SMA)是由运动神经元存活基因(SMN1)的缺失或突变引起的。其高度同源的拷贝SMN2存在于所有SMA病例中，是一种表型修饰物。有一些典型的SMA患者的无症状兄弟姐妹具有SMN1纯合子缺失的情况，就像他们有症状的兄弟姐妹一样。纤溶酶原3(PLS3)在女性淋巴母细胞中过表达，被认为是SMA的遗传修饰基因。我们研究了四个SMA基因座不一致的同胞在西班牙SMA家族中的PLS3表达。我们排除了PLS3作为一个可能的修饰语，在我们的两个家庭中有女性不和谐的兄弟姐妹。在剩下的两个中，我们观察到PLS3在男性和女性不和谐的兄弟姐妹中的表达略有差异。事实上，我们发现淋巴母细胞和外周血中PLS3的表达水平比成纤维细胞低12到200倍。这些发现值得对这些患者的诱导多潜能干细胞来源的运动神经元进行进一步的研究。(C)2011爱思唯尔B.V.保留所有权利。
Spinal muscular atrophy (SMA) is caused by loss or mutations of the survival motor neuron I gene (SMN1). Its highly homologous copy, SMN2, is present in all SMA cases and is a phenotypic modifier. There are cases where asymptomatic siblings of typical SMA patients possess a homozygous deletion of SMN1 just like their symptomatic brothers or sisters. Plastin 3 (PLS3) when over expressed in lymphoblasts from females has been suggested to act as a genetic modifier of SMA.We studied PLS3 expression in four Spanish SMA families with discordant siblings haploidentical for the SMA locus. We excluded PLS3 as a possible modifier in two of our families with female discordant siblings. In the remaining two, we observed small differences in PLS3 expression between male and female discordant siblings. Indeed, we found that the values of PLS3 expression in lymphoblasts and peripheral blood ranged from 12 to 200-fold less than those in fibroblasts. These findings warrant further investigation in motor neurons derived from induced pluripotential stem cells of these patients. (C) 2011 Elsevier B.V. All rights reserved.