Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs
Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs
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DOI：
10.1111/j.1399-0004.2010.01498.x
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发表时间：
2011-01-01
影响因子：
3.5
通讯作者：
Alkuraya, F. S.
中科院分区：
文献类型：
--
作者：
Shaheen, R.;Al-Dirbashi, O. Y.;Alkuraya, F. S.
过氧化物酶体是单膜结合的细胞器，其进行关键的代谢反应，其扰动导致称为过氧化物酶体病症（PD）的一系列临床表型。在这项中东地区同类研究中规模最大的研究中，我们试图在临床，生化和分子水平上全面描述这些罕见疾病。在两年的时间里，我们招募了17名患者，代表16个阿拉伯家庭。12例患者观察到Zellweger谱表型，其余5例患者观察到点状肢根软骨发育不良表型。我们表明，纯合性定位是一种具有成本效益的策略，使潜在的遗传缺陷的识别在100%的情况下。通过免疫荧光和互补测定证实了所鉴定的突变的致病性。我们证实了PD在我们人群中的遗传异质性，扩大了致病等位基因的库，并得出了一些表型/基因型相关性。
Peroxisomes are single membrane-bound cellular organelles that carry out critical metabolic reactions perturbation of which leads to an array of clinical phenotypes known as peroxisomal disorders (PD). In this study, the largest of its kind in the Middle East, we sought to comprehensively characterize these rare disorders at the clinical, biochemical and molecular levels. Over a 2-year period, we have enrolled 17 patients representing 16 Arab families. Zellweger-spectrum phenotype was observed in 12 patients and the remaining 5 had the rhizomelic chondrodysplasia punctata phenotype. We show that homozygosity mapping is a cost-effective strategy that enabled the identification of the underlying genetic defect in 100% of the cases. The pathogenic nature of the mutations identified was confirmed by immunofluorescence and complementation assays. We confirm the genetic heterogeneity of PD in our population, expand the pool of pathogenic alleles and draw some phenotype/genotype correlations.