University of Amsterdam, Academic Medical Center, Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Amsterdam, The Netherlands.
Hum Mutat. 2010 Jan;31(1):E1058-70. doi: 10.1002/humu.21153.
The autosomal recessive Zellweger syndrome spectrum (ZSS) disorders comprise a main subgroup of the peroxisome biogenesis disorders. The ZSS disorders can be caused by mutations in any of 12 different currently identified PEX genes resulting in severe, often lethal, multi-systemic disorders. Defects in the PEX6 gene are the second most common cause for ZSS disorders. The encoded protein PEX6 belongs to the AAA ATPase family and contains two AAA cassettes and an AAA protein family signature. The PEX6 gene consists of 17 exons and previously mutations in the PEX6 gene were found to be scattered over all exons. We developed a post-PCR high-resolution melting (HRM) curve assay to scan the PEX6 gene for potential sequence variations followed by selective sequencing to identify these. We analyzed the PEX6 genes of 75 patients assigned to the PEX6 complementation group. We identified a total of 77 different mutations of which 47 mutations have not been reported previously, and 14 polymorphic variants.
常染色体隐性 Zellweger 综合征谱（ZSS）疾病是过氧化物酶体生物发生障碍的主要亚群之一。ZSS 疾病可由 12 种不同的 PEX 基因中的任何一种突变引起，导致严重的、常常致命的多系统疾病。PEX6 基因突变是 ZSS 疾病的第二大常见原因。编码的 PEX6 蛋白属于 AAA ATP 酶家族，包含两个 AAA 盒和一个 AAA 蛋白家族特征。PEX6 基因由 17 个外显子组成，先前发现 PEX6 基因中的突变分散在所有外显子中。我们开发了一种聚合酶链反应后高分辨率熔解（HRM）曲线分析，以扫描 PEX6 基因中潜在的序列变异，然后进行选择性测序以识别这些变异。我们分析了属于 PEX6 互补组的 75 名患者的 PEX6 基因。我们共发现了 77 种不同的突变，其中 47 种突变以前没有报道过，还有 14 种多态性变异。
