Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency
Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency
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DOI：
10.1210/jc.2003-031021
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Auchus, RJ
中科院分区：
文献类型：
--
作者：
Costa-Santos, M;Kater, CE;Auchus, RJ
我们进行了分子遗传学分析的24名受试者从19个家庭与17-羟化酶缺乏症在巴西。在7个新的CYP 17突变中，2个（W 406 R和R362 C）分别占突变等位基因的50%和32%。在COS-7细胞和酵母微粒体中研究时，这两种突变都是完全无活性的;然而，受试者的表型特征各不相同。一些46，XY个体与这些基因型有模糊的生殖器，和其他科目有正常的血压和/或血清钾。我们发现突变W 406 R和R362 C主要是在西班牙和葡萄牙血统的家庭，分别，这表明两个独立的创始人的影响，有助于增加巴西的17-羟化酶缺乏症的患病率。突变Y329 D和P428 L保留了微量活性，但具有这些突变的两个个体患有严重的高血压和低钾血症。携带突变Y329 D的46，XX女性达到坦纳5期，而携带突变P428 L的46，XY受试者仍为性幼稚。高血压、低钾血症、17-脱氧类固醇过量和性类固醇缺乏的严重程度各不相同，即使在CYP 17蛋白完全失活的患者中也是如此。自发性发育仅发生在46，XX女性部分缺陷。我们的结论是，其他因素，除了CYP 17基因型，有助于17-羟化酶缺乏症的个体患者的表型。
We performed molecular genetic analysis of 24 subjects from 19 families with 17-hydroxylase deficiency in Brazil. Of 7 novel CYP17 mutations, 2 (W406R and R362C) account for 50% and 32% of the mutant alleles, respectively. Both mutations were completely inactive when studied in COS-7 cells and yeast microsomes; however, phenotypic features varied among subjects. Some 46,XY individuals with these genotypes had ambiguous genitalia, and other subjects had normal blood pressure and/or serum potassium. We found mutations W406R and R362C principally in families with Spanish and Portuguese ancestry, respectively, suggesting that two independent founder effects contribute to the increased prevalence of 17-hydroxylase deficiency in Brazil. Mutations Y329D and P428L retained a trace of activity, yet the two individuals with these mutations had severe hypertension and hypokalemia. The 46,XX female with mutation Y329D reached Tanner stage 5, whereas the 46, XY subject with mutation P428L remained sexually infantile. The severity of hypertension, hypokalemia, 17-deoxysteroid excess, and sex steroid deficiency varied, even among patients with completely inactive CYP17 protein(s). Spontaneous sexual development occurred only in 46, XX females with partial deficiencies. We conclude that other factors, in addition to CYP17 genotype, contribute to the phenotype of individual patients with 17-hydroxylase deficiency.