Waterham Hans R, Ebberink Merel S
University of Amsterdam, the Netherlands.
Biochim Biophys Acta. 2012 Sep;1822(9):1430-41. doi: 10.1016/j.bbadis.2012.04.006. Epub 2012 Apr 25.
Human peroxisome biogenesis disorders (PBDs) are a heterogeneous group of autosomal recessive disorders comprised of two clinically distinct subtypes: the Zellweger syndrome spectrum (ZSS) disorders and rhizomelic chondrodysplasia punctata (RCDP) type 1. PBDs are caused by defects in any of at least 14 different PEX genes, which encode proteins involved in peroxisome assembly and proliferation. Thirteen of these genes are associated with ZSS disorders. The genetic heterogeneity among PBDs and the inability to predict from the biochemical and clinical phenotype of a patient with ZSS which of the currently known 13 PEX genes is defective, has fostered the development of different strategies to identify the causative gene defects. These include PEX cDNA transfection complementation assays followed by sequencing of the thus identified PEX genes, and a PEX gene screen in which the most frequently mutated exons of the different PEX genes are analyzed. The benefits of DNA testing for PBDs include carrier testing of relatives, early prenatal testing or preimplantation genetic diagnosis in families with a recurrence risk for ZSS disorders, and insight in genotype-phenotype correlations, which may eventually assist to improve patient management. In this review we describe the current status of genetic analysis and the molecular basis of PBDs.
人类过氧化物酶体生物发生障碍（PBDs）是一组常染色体隐性遗传疾病，具有异质性，由两种临床上不同的亚型组成：泽尔韦格综合征谱系（ZSS）疾病和1型点状软骨发育不良（RCDP）。PBDs是由至少14种不同的PEX基因中的任何一种缺陷引起的，这些基因编码参与过氧化物酶体组装和增殖的蛋白质。其中13个基因与ZSS疾病相关。PBDs之间的遗传异质性以及无法从ZSS患者的生化和临床表型预测目前已知的13个PEX基因中的哪一个有缺陷，促使人们开发不同的策略来识别致病基因缺陷。这些策略包括PEX cDNA转染互补分析，随后对由此鉴定的PEX基因进行测序，以及对不同PEX基因最常发生突变的外显子进行分析的PEX基因筛查。PBDs的DNA检测的好处包括对亲属进行携带者检测、对有ZSS疾病复发风险的家庭进行早期产前检测或植入前基因诊断，以及深入了解基因型与表型的相关性，这最终可能有助于改善患者管理。在这篇综述中，我们描述了PBDs的遗传分析现状和分子基础。
