Peroxisomal bifunctional protein deficiency revisited: Resolution of its true enzymatic and molecular basis
Peroxisomal bifunctional protein deficiency revisited: Resolution of its true enzymatic and molecular basis
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DOI：
10.1086/302180
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发表时间：
1999-01-01
影响因子：
9.8
通讯作者：
Wanders, RJA
中科院分区：
文献类型：
--
作者：
van Grunsven, EG;van Berkel, E;Wanders, RJA
在过去的几年中，许多患者已被描述谁有一个未知的原因在过氧化物酶体β-氧化途径的缺陷。互补分析已经由不同的小组进行，以确定患者之间的遗传异质性的程度。这些研究是基于使用两种已建立的细胞系，一种缺乏酰基辅酶A氧化酶，一种缺乏L-双功能蛋白（L-BP），他们表明，大多数患者属于L-BP缺乏组。然而，对患者中编码L-BP的cDNA的分子分析未能显示任何突变。最近发现的一种新的D-特异性双功能蛋白（D-BP）促使我们重新调查原来的病人假定L-BP缺乏症。在合作的努力下，我们现在发现，在这个病人的色调缺陷是在D-BP的水平，而不是在L-BP的水平。我们的研究结果表明，大多数（如果不是全部）被诊断为L-BP的患者实际上是D-BP缺乏。我们测试了这一假设在9例患者的条件被诊断为L-BP缺乏症的基础上互补分析，并发现明确的突变的D-BP cDNA从所有患者。
In the past few years, many patients have been described who have a defect of unknown origin in the peroxisomal beta-oxidation pathway. Complementation analysis has been done by various groups to establish the extent of the genetic heterogeneity among the patients. These studies were based on the use of two established cell lines, one with a deficiency of acyl-CoA oxidase and one with a deficiency of L-bifunctional protein (L-BP), and they showed that most patients belong to the L-BP-deficient group. However, molecular analysis of the cDNA encoding L-BP in patients failed to show any mutations. The recent identification of a new D-specific bifunctional protein (D-BP) prompted us to reinvestigate the original patient with presumed L-BP deficiency. In a collaborative effort, we have now found that the hue defect in this patient is at the level of the D-BP and not at the Level of the L-BP. Our results suggest that most, if not all, patients whose condition has been diagnosed as L-BP are, in fact, D-BP deficient. We tested this hypothesis in nine patients whose condition was diagnosed as L-BP deficiency on the basis of complementation analysis and found clear-cut mutations in the D-BP cDNA from all patients.