突变SRD5B1 (AKR1D1)基因编码三角洲(4)3-oxosteroid 5 beta-reductase,肝炎和肝衰竭的初级阶段。
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《世界报》哈,奶油EJ,花束J,杜兰M, Overmars H,扰码PJ,克莱顿PT
突变SRD5B1 (AKR1D1)基因编码三角洲(4)3-oxosteroid 5 beta-reductase,肝炎和肝衰竭的初级阶段。
肠道。2003年10月,52 (10):1494 - 9。
- PubMed ID
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12970144 (在PubMed]
- 文摘
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背景:一大群在婴儿期排泄胆汁郁积的肝病患者,作为主要的尿胆汁酸,甘氨酸、牛磺酸的轭合物7 alpha-hydroxy-3-oxo-4-cholenoic酸和7α,12 alpha-dihydroxy-3-oxo-4-cholenoic酸。已经提出了一些(但不是所有)的突变基因编码三角洲(4)3-oxosteroid 5 beta-reductase (SRD5B1;AKR1D1,人类604741年)。目的:我们的目的是确定SRD5B1基因的突变的病人胆酸和鹅去氧胆酸缺失或出现在低浓度在血浆和尿液,因为这些似乎缺乏强有力的候选基因5 beta-reductase。病人和主题:我们研究三个新生儿发病淤胆型肝病患者和正常gamma-glutamyl转肽酶在他3-oxo-delta(4)胆汁酸主要胆汁酸在尿液和血浆和饱和胆汁酸在低浓度或检测不到。任何基地变化中发现SRD5B1寻求父母和兄弟姐妹和50种族匹配的对照组。方法:从血液中提取DNA的9个外显子SRD5B1被放大和测序。限制性内切酶被用来屏幕的DNA的父母,兄弟姐妹,和控制。结果:SRD5B1基因的突变被发现在所有三个孩子。病人女士为错义突变纯合子(662 C > T)导致Pro198Leu氨基酸替换; patient BH was homozygous for a single base deletion (511 delT) causing a frame shift and a premature stop codon in exon 5; and patient RM was homozygous for a missense mutation (385 C>T) causing a Leu106Phe amino acid substitution. All had liver biopsies showing a giant cell hepatitis; in two, prominent extramedullary haemopoiesis was noted. MS was cured by treatment with chenodeoxycholic acid and cholic acid; BH showed initial improvement but then deteriorated and required liver transplantation; RM had advanced liver disease when treatment was started and also progressed to liver failure. CONCLUSIONS: Analysis of blood samples for SRD5B1 mutations can be used to diagnose genetic 5beta-reductase deficiency and distinguish these patients from those who have another cause of 3-oxo-delta(4) bile aciduria, for example, severe liver damage. Patients with genetic 5beta-reductase deficiency may respond well to treatment with chenodeoxycholic acid and cholic acid if liver disease is not too advanced.