Kruger W D, Cox D R
Department of Genetics, Stanford University, School of Medicine, CA 94305, USA.
Hum Mol Genet. 1995 Jul;4(7):1155-61. doi: 10.1093/hmg/4.7.1155.
Mutations in the human cystathionine beta-synthase (CBS) gene are known to cause homocystinuria and may also be a significant risk factor for premature atherosclerosis. We have previously shown that the human CBS protein can substitute for the endogenous yeast CBS protein in Saccharomyces cerevisiae. We now show that expression of three different CBS mutants known to be associated with reduced enzyme activity in humans fail to complement growth in the yeast assay. In addition, we have used the yeast CBS assay to identify eight mutant CBS alleles in cell lines from patients with CBS deficiency. These mutant alleles include two previously identified and five novel CBS mutations. Our results also demonstrate that the yeast CBS assay can detect a large percentage of individuals heterozygous for mutations in CBS. This system should be useful in determining the relationship between CBS mutations and human disease.
已知人类胱硫醚β-合酶（CBS）基因突变会导致同型胱氨酸尿症，并且可能也是过早发生动脉粥样硬化的一个重要风险因素。我们之前已经表明，人类CBS蛋白可以替代酿酒酵母中的内源性酵母CBS蛋白。我们现在表明，已知与人类酶活性降低相关的三种不同CBS突变体的表达在酵母检测中无法补充生长。此外，我们已经使用酵母CBS检测在CBS缺乏症患者的细胞系中鉴定出八个突变CBS等位基因。这些突变等位基因包括两个先前鉴定出的和五个新的CBS突变。我们的结果还表明，酵母CBS检测可以检测出很大比例的CBS突变杂合个体。该系统在确定CBS突变与人类疾病之间的关系方面应该是有用的。
