van Grunsven E G, van Berkel E, Mooijer P A, Watkins P A, Moser H W, Suzuki Y, Jiang L L, Hashimoto T, Hoefler G, Adamski J, Wanders R J
Laboratory for Genetic Metabolic Diseases, Department of Clinical Chemistry, University of Amsterdam, The Netherlands.
Am J Hum Genet. 1999 Jan;64(1):99-107. doi: 10.1086/302180.
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 true 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.
在过去几年里，已描述了许多患者，他们在过氧化物酶体β-氧化途径中存在不明来源的缺陷。多个研究小组进行了互补分析，以确定患者之间遗传异质性的程度。这些研究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，另一种缺乏l-双功能蛋白（l-BP），结果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进行分子分析未发现任何突变。最近新发现的一种d特异性双功能蛋白（d-BP）促使我们重新研究最初被认为是l-BP缺乏的患者。通过合作，我们现在发现该患者的真正缺陷在于d-BP水平，而非l-BP水平。我们的结果表明，大多数（如果不是全部）被诊断为l-BP缺乏的患者实际上是d-BP缺乏。我们在9名根据互补分析被诊断为l-BP缺乏的患者中检验了这一假设，发现所有患者的d-BP cDNA中都有明确的突变。
