Reply: chorea-acanthocytosis with an autosomal-dominant trait
Reply: chorea-acanthocytosis with an autosomal-dominant trait
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答复：具有常染色体显性遗传特征的舞蹈病-棘红细胞增多症
DOI：
10.1007/s00401-008-0444-5
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发表时间：
2008
影响因子：
12.7
通讯作者：
M. Yamada
中科院分区：
文献类型：
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作者：
C. Ishida;S. Saiki;M. Yamada
首先，我们要感谢Bader等人。[1]他们对我们的论文“伴有VPS13A突变的常染色体显性舞蹈病棘红细胞增多症（ChAc）的神经病理学研究”的评论[3]。根据他们的评论，我们与该家系相关的遗传数据尚未完全排除VPS13A基因可能存在另一种突变的可能性[4]。在遗传数据的研究中，我们对ChAc患者的cDNA进行了突变分析，因此我们认为Bader等人对遗传分析的评论是公平合理的。我们也感谢他们对我们报告中描述的ChAc骨骼肌生化分析的评论[5]。遗憾的是，由于缺乏肌肉、脑和其他器官的样品，我们无法通过Western印迹分析进行chorein表达测定。我们的实验室目前正在对paraYn包埋的脑切片进行免疫组织化学分析[3]。正如Bader et al. [1]因此，需要使用其他突变筛查方法和蛋白质印迹分析以及神经病理学和免疫组织化学研究对本家族的其他成员进行进一步研究。然而，我们的病人的父亲和其他家庭成员表现出一些ChAc的临床表现和神经系统异常是从父母遗传给孩子。这些临床数据与以往报道的常染色体隐性ChAc不同。因此，我们诊断我们的尸检病例和他的家人具有常染色体显性遗传特征。作为未发表的数据，Bader等人。[1]注意到在三个遗传学证实的ChAc患者的两个父母的红细胞膜显示正常chorein表达。他们推测，单个突变基因的影响因此可能通过调节VPS13A表达途径来补偿。然而，为了证实他们的假设，需要进一步的chorein表达数据在其他器官受影响的ChAc患者，如尾状核，壳核，骨骼肌。佐野等人[2]报告说他们的杂合子突变携带者有一些神经异常。该家系的数据提示，即使是一个突变也可能导致ChAc患者的神经功能障碍。Velayos-Baeza等人[6]检查了用VPS13A构建体瞬时转染的细胞或用抗软骨素抗体免疫染色的细胞中的软骨素分布。然而，没有与其他细胞结构共定位，因此该蛋白的细胞内功能仍不清楚。作者还使用一些突变的chorein质粒进行过表达实验。在他们的研究中，亚细胞分布变化是异质的，这意味着每个突变的chorein可能对细胞产生不同的影响。然而，额外的实验
First, we would like to thank Bader et al.[1] for their comments on our paper,“A neuropathological study of autosomal-dominant chorea-acanthocytosis (ChAc) with a mutation of VPS13A”[3]. According to their comments, our genetic data associated with the pedigree have not completely excluded the possibility that there may be another mutation in the VPS13A gene [4]. In the study of the genetic data, we performed mutation analysis with cDNA from ChAc patients, and so we feel that the comment of Bader et al. on the genetic analyses is fair and reasonable. We are also grateful for their comments on the biochemical analysis of skeletal muscles in ChAc described in our report [5]. Unfortunately, we could not perform chorein expression assay by Western blotting analysis because of a lack of samples of muscle, brain and other organs. Immunohistochemical analysis of paraYn-embedded brain sections for chorein is currently underway in our laboratory [3]. As suggested by Bader et al.[1], further studies are needed in other members of the present family using other mutation screening methods and Western blotting analyses, as well as neuropathological and immunohistochemical studies. However, our patient’s father and the other family members showed some clinical manifestations of ChAc and the neurological abnormalities were inherited from the parent to the child. These clinical data were different from those of previous reports regarding autosomal-recessive ChAc. Therefore, we diagnosed our autopsy case and his family as having an autosomal-dominant trait. As unpublished data, Bader etal.[1] noted that red blood cell membranes in two parents of three genetically confirmed ChAc patients showed normal chorein expression. They speculated that the effects of a single mutated gene are thus likely compensated by regulatory VPS13A expression pathway. However, to confirm their hypothesis, further chorein expression data are needed in other organs affected in ChAc patients, such as the caudate nucleus, putamen, and skeletal muscles. Sano et al.[2] reported that their heterozygous mutation carriers had some neurological abnormalities. The data in this family suggested that even a single mutation could contribute to neuronal dysfunction in ChAc patients.Chorein function has not been characterized suYciently. Velayos-Baeza et al.[6] examined chorein distribution in cells transiently transfected with VPS13A constructs or cells immunostained with anti-chorein antibody. However, there was no colocalization with other cellular structures so that the intracellular function of the protein remains unclear. The authors also performed overexpression experiments using some mutant chorein plasmids. In their study, the subcellular distribution changes were heterogeneous, implying that each mutated chorein may have a different effect on the cell. However, additional experiments are
舞蹈病棘红细胞增多症的原发性骨骼肌参与
DOI：
--
发表时间：
2007
期刊：
Mov Disord 22
影响因子：
--
作者：
Nakajima H;Hosokawa T;Sugino M;Kimura F;Hanafusa T;Ikemoto T;Shimizu A.;Saiki S
通讯作者：
Saiki S