Kraus J P
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
J Inherit Metab Dis. 1994;17(4):383-90. doi: 10.1007/BF00711354.
Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria in humans. The human gene maps to chromosome 21q22.3 and encodes the CBS subunit of 551 amino acid residues (63kDa). CBS, a tetramer of these subunits, binds its two substrates, homocysteine and serine, and three additional ligands: pyridoxal 5'-phosphate, S-adenosylmethionine, and haem. Screening for mutations by expressing patient cDNA segments in E. coli permitted us to separate the parental CBS alleles, localize each mutation within one third of the cDNA, and functionally analyse the mutant protein. Using this method we identified the first 14 mutations in homocystinuria. The most common mutation in patients of predominantly 'Celtic' origin is the G919A transition which substitutes serine for glycine 307.
胱硫醚β-合酶（CBS）缺乏症是人类高胱氨酸尿症最常见的病因。人类基因定位于21号染色体q22.3，编码由551个氨基酸残基（63kDa）组成的CBS亚基。CBS由这些亚基组成四聚体，可结合其两种底物——同型半胱氨酸和丝氨酸，以及另外三种配体：磷酸吡哆醛、S-腺苷甲硫氨酸和血红素。通过在大肠杆菌中表达患者cDNA片段来筛选突变，使我们能够分离亲本CBS等位基因，将每个突变定位在cDNA的三分之一范围内，并对突变蛋白进行功能分析。使用这种方法，我们在高胱氨酸尿症中鉴定出了首批14种突变。在主要为“凯尔特”血统的患者中，最常见的突变是G919A转换，该突变使307位的甘氨酸被丝氨酸替代。
