A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts
A PEX10 defect in a patient with no detectable defect in peroxisome assembly or metabolism in cultured fibroblasts
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DOI：
10.1007/s10545-008-0969-8
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发表时间：
2009-01
影响因子：
4.2
通讯作者：
S. Steinberg;A. Snowden;Nancy Braverman;Li Chen;P. A. Watkins;Peter E. Clayton;K. Setchell;J E Heubi;Gerald V. Raymond;A. B. Moser;Hugo W. Moser
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文献类型：
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作者：
S. Steinberg;A. Snowden;Nancy Braverman;Li Chen;P. A. Watkins;Peter E. Clayton;K. Setchell;J E Heubi;Gerald V. Raymond;A. B. Moser;Hugo W. Moser
Zellweger谱系疾病是通过血液、尿液和培养成纤维细胞的生化检测和PEX基因突变鉴定来诊断的。在大多数情况下，对成纤维细胞的研究证实了在体液中获得的结果。1996年，克莱顿和他的同事描述了一名10岁的女孩，根据升高的胆汁酸代谢物和植酸盐，有证据表明她患有过氧化物酶紊乱。当时，无法区分她是否患有ZSD或单一的过氧酶体蛋白缺陷。我们实验室的研究表明，她也有血浆哌替酸升高，支持以前的诊断。尽管在血液中检测到异常代谢物(植酸盐、胆汁酸中间体和哌替酯)，但对成纤维细胞中的多个过氧体途径的分析得出了正常的结果。此外，她的临床表型比通常与ZSD有关的症状要轻。由于互补分析无法确定基因缺陷，我们按照PEX基因筛选算法(PGS)对该患者进行了筛查。PGS为PEX基因外显子测序提供了一个独立于互补分析的模板。在PEX10中发现了两个突变，一个是从她父亲那里遗传的移码突变，另一个是在另一个等位基因上的保守功能区发生新呕吐突变。此病例强调了分子分析对于诊断ZSD谱系中较轻的患者可能是必不可少的。此外，它支持这样的概念，即某些组织受某些PEX基因缺陷的影响比大脑和肝脏小。
Zellweger spectrum disorders (ZSD) are diagnosed by biochemical assay in blood, urine and cultured fibroblasts and PEX gene mutation identification. In most cases studies in fibroblasts corroborate results obtained in body fluids. In 1996 Clayton and colleagues described a 10-year old girl with evidence of a peroxisome disorder, based on elevated bile acid metabolites and phytanate. At the time it was not possible to distinguish whether she had a ZSD or a single peroxisomal protein defect. Studies in our laboratory showed that she also had elevated plasma pipecolate, supporting the former diagnosis. Despite the abnormal metabolites detected in blood (phytanate, bile acid intermediates and pipecolate), analysis of multiple peroxisomal pathways in fibroblasts yielded normal results. In addition, she had a milder clinical phenotype than usually associated with ZSD. Since complementation analysis to determine the gene defect was not possible, we screened this patient following the PEX Gene Screen algorithm (PGS). The PGS provides a template for sequencing PEX gene exons independent of complementation analysis. Two mutations inPEX10were identified, a frameshift mutation inherited from her father and ade novomissense mutation in a conserved functional domain on the other allele. This case highlights that molecular analysis may be essential to the diagnosis of patients at the milder end of the ZSD spectrum. Furthermore, it supports the concept that some tissues are less affected by certain PEX gene defects than brain and liver.