Chronological changes in prosaposin in the developing rat brain
Chronological changes in prosaposin in the developing rat brain
复制标题
发育中的大鼠大脑中前塞塞辛的时间变化
DOI：
10.1016/j.neures.2011.06.001
复制
发表时间：
2011
期刊：
影响因子：
2.9
通讯作者：
et al
中科院分区：
文献类型：
--
作者：
Xue;et al
棘细胞舞蹈症是一种罕见的常染色体隐性遗传性神经退行性疾病，由编码舞蹈素的空泡蛋白分类13同源A基因(VPS13A)功能缺失突变引起。它的特征是成人起病的舞蹈症、外周棘细胞和神经精神症状。在本研究中，我们对CHAC患者的VPS13A基因进行了全面的突变筛查，包括测序和拷贝数变异(CNV)分析。对35例CHAC患者的VPS13A基因全部73个外显子及其侧翼区进行了测序。为了检测CNV，我们还对仅检测到一个杂合子突变的患者进行了VPS13A基因的实时定量PCR和长程PCR分析。我们鉴定了36个致病突变，其中20个以前没有报道，包括两个新的CNV。此外，我们还用免疫印迹法检测了16例患者的Chorein基因的表达。这表明在病原性突变的患者中完全没有舞蹈素。这一全面的筛查为CHAC的分子诊断提供了一种准确而有用的方法。©2011 Wiley-Liss，Inc.
Chorea‐acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult‐onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of theVPS13Agene in ChAc patients. All 73 exons and flanking regions ofVPS13Awere sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real‐time quantitative PCR and long‐range PCR analyses for theVPS13Agene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc. © 2011 Wiley‐Liss, Inc.