功能的后果七新颖的CYP11B1基因的突变:四个突变与nonclassic和三个突变导致经典11{β}羟化酶缺乏症。
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Parajes年代,Loidi L, Reisch N, V,迪尔玫瑰,Hampel R, Quinkler M,康威GS, Castro-Feijoo L, Araujo-Vilar D, Pombo M, Dominguez F,威廉姆斯EL科尔TR,柯克JM, Kaminsky E, Rumsby G, Arlt W,克朗N
功能的后果七新颖的CYP11B1基因的突变:四个突变与nonclassic和三个突变导致经典11{β}羟化酶缺乏症。
中国性金属底座。2010年2月,95 (2):779 - 88。doi: 10.1210 / jc.2009 - 0651。Epub 2010 1月20。
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20089618 (在PubMed]
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背景:类固醇11 beta-hydroxylase (CYP11B1)缺乏症(11 ohd)是第二个最常见的先天性肾上腺增生(CAH)。11例nonclassic ohd非常罕见而nonclassic的发病率21-hydroxylase缺乏症。目的:这项研究的目的是分析功能的后果七小说的CYP11B1基因突变(p。M88I, p。W116G, p。P159L, p。A165D, p。K254_A259del, p。R366C p.T401A)患者中发现的三个经典11 ohd两nonclassic 11 ohd,患者和三的CYP11B1基因突变杂合的运营商。方法:我们进行了功能性研究雇佣COS7细胞体外表达系统比较野生型(WT)和突变的CYP11B1活动。突变体进行计算机三维模型的CYP11B1蛋白质。结果:所有的突变(p。W116G, p。A165D, p。K254_A259del) found in patients with classic 11OHD have absent or very little 11beta-hydroxylase activity relative to WT. The mutations detected in patients with nonclassic 11OHD showed partial functional impairment, with one patient being homozygous (p.P159L; 25% of WT) and the other patient compound heterozygous for a novel mild p.M88I (40% of WT) and the known severe p.R383Q mutation. The two mutations detected in heterozygous carriers (p.R366C, p.T401A) also reduced CYP11B1 activity by 23 to 37%, respectively. CONCLUSION: Functional analysis results allow for the classification of novel CYP11B1 mutations as causative for classic and nonclassic 11OHD, respectively. Four partially inactivating mutations are predicted to result in nonclassic 11OHD. These findings double the number of mild CYP11B1 mutations previously described as associated with mild 11OHD. Our data are important to predict phenotypic expression and provide important information for clinical and genetic counseling in 11OHD.