The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders, in the Zellweger syndrome spectrum
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders, in the Zellweger syndrome spectrum
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DOI：
10.1016/j.ymgme.2004.08.008
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发表时间：
2004-11-01
影响因子：
3.8
通讯作者：
Braverman, N
中科院分区：
文献类型：
--
作者：
Steinberg, S;Chen, L;Braverman, N
Zellweger综合征谱系（PBD-ZSS）中的过氧化物酶体生物发生障碍是由至少12个正常细胞器组装所需的PEX基因缺陷引起的。临床和生化特征继续被可靠地用于将患者分配到这种一般疾病类别。然而，精确识别遗传缺陷对于携带者检测和早期产前诊断是很重要的。分子分析有可能扩大PBD的临床范围，也可能提供与预后和未来治疗干预相关的数据。然而，涉及的大量基因迄今为止阻碍了快速突变鉴定。作为回应，我们开发了PEX基因筛选，这是一种系统筛选PBD-ZSS中最常见缺陷的六个PEX基因的外显子的算法。我们利用基因组DNA的PCR扩增和测序技术筛选91例未分类的PBD-ZSS患者的PEX1、PEX26、PEX6、PEX12、PEX10和PEX2基因突变。每位患者最多14次反应中，79%的患者发现了病理突变，54%的患者发现了两个突变等位基因。总共鉴定出25个新的突变。不同PEX基因缺陷患者的比例与之前通过互补分析确定的频率相关。因此，这种系统的、分层的突变鉴定方法是快速鉴定疑似PBD-ZSS疾病的分子病因的有价值的工具。(C) 2004爱思唯尔公司版权所有。
Peroxisome biogenesis disorders in the Zellweger syndrome spectrum (PBD-ZSS) are caused by defects in at least 12 PEX genes required for normal organelle assembly. Clinical and biochemical features continue to be used reliably to assign patients to this general disease category. Identification of the precise genetic defect is important, however, to permit carrier testing and early prenatal diagnosis. Molecular analysis is likely to expand the clinical spectrum of PBD and may also provide data relevant to prognosis and future therapeutic intervention. However, the large number of genes involved has thus far impeded rapid mutation identification. In response, we developed the PEX Gene Screen, an algorithm for the systematic screening of exons in the six PEX genes most commonly defective in PBD-ZSS. We used PCR amplification of genomic DNA and sequencing to screen 91 unclassified PBD-ZSS patients for mutations in PEX1, PEX26, PEX6, PEX12, PEX10, and PEX2. A maximum of 14 reactions per patient identified pathological mutations in 79% and both mutant alletes in 54%. Twenty-five novel mutations were identified overall. The proportion of patients with different PEX gene defects correlated with frequencies previously identified by complementation analysis. This systematic, hierarchical approach to mutation identification is therefore a valuable tool to identify rapidly the molecular etiology of suspected PBD-ZSS disorders. (C) 2004 Elsevier Inc. All rights reserved.