四个小说突变胱硫醚beta-synthase基因:效应相关的第二个突变homocystinuric表现型的严重性。
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德·弗兰R,克劳斯E, Kozich V, Sebastio G,克劳斯JP
四个小说突变胱硫醚beta-synthase基因:效应相关的第二个突变homocystinuric表现型的严重性。
哼Mutat。1999; 13 (6): 453 - 7。
- PubMed ID
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10408774 (在PubMed]
- 文摘
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高胱氨酸尿由于胱硫醚beta-synthase (CBS)缺乏是经常引起的错义突变。在这篇文章中,我们报告四个小说在CBS基因错义突变:172 c - - > T (R58W)与cis A114V;- - > 376 G (M126V);904 g - - > (E302K);和1006 c - - > T (R336C)。CBS活动相应的突变体酶在大肠杆菌表达是大大降低,证实这些突变的致病性。西方的分析表明,R58W + A114V和M126V突变酶在大肠杆菌不稳定,而E302K子单元部分退化较短的产品。使用定点诱变我们发现包含R58W或CBS A114V作为唯一突变了正常活动的18%和46%,分别。两种突变形式的CBS在大肠杆菌稳定。当这两个突变表达cis,合成突变蛋白表现出1.3%的控制活动。 All these in vitro results were in good agreement with the clinical manifestation in these patients. The Italian patient 2241, an A114V+R58W/M126V compound heterozygote, exhibited severe pyridoxine nonresponsive homocystinuria, while another Italian patient 2242, with an A114V/E302K genotype, responded to pyridoxine treatment and had a much milder phenotype. The third patient 3064, an English compound heterozygote for two severe mutations R336C and G307S, was B6 nonresponsive. This report of a ninth homocystinuric allele carrying two mutations in cis raises the possibility that double mutant alleles may be underestimated in homocystinuric patients. In this context, a search for additional mutations in cis may sometimes be necessary to establish a good genotype-phenotype relationship.