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>Deficiência combinada de 17 alfa-hidroxilase/17,20 liase devido a duplicação de 25 PB (NT 4157-4181) no éxon 5 do CYP17 resultando em parada prematura de leitura predita por modelagem molecular
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Deficiência combinada de 17 alfa-hidroxilase/17,20 liase devido a duplicação de 25 PB (NT 4157-4181) no éxon 5 do CYP17 resultando em parada prematura de leitura predita por modelagem molecular
Combined 17alpha-hydroxylase/17,20-lyase deficiency is a rare, autosomal recessive form of congenital adrenal hyperplasia characterized by the coexistence of hypertension, caused by the hyperproduction of mineralocorticoid precursors and DSD in males and sexual infantilism in females, due to impaired production of sex hormones. Several CYP17 mutations resulting in 17alpha-hydroxylase/17,20-lyase deficiency have been reported previously. In the present study, we described a novel CYP17 mutation in two Brazilian sisters with primary amenorrhea, 46,XY karyotype, high basal levels of progesterone (3.4-4.9 ng/mL) and hypokalemic hypertension born to consanguineous parents. After PCR and automatic sequencing of CYP17 coding region, 25 bp duplication at exon 5 was found in the patients. This duplication started at codon 318 resulting in a premature stop codon at position 320 resulting in an ineffective and truncated protein and in accordance with the molecular modeling of P450c17. Therefore we expanded the repertoire of CYP17 mutations describing the largest duplication found in this gene in both sisters, with a clinical phenotype of combined 17alpha-hydroxylase/17,20-lyase deficiency and emphasizes the importance of the P450c 17 molecular modeling to predict the functional effect of these mutations.
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机译:合并的17α-羟化酶/ 17,20-裂合酶缺乏症是一种罕见的常染色体隐性遗传形式的先天性肾上腺皮质增生,其特征是高血压并存,这是由于男性中盐皮质激素前体和DSD的过量产生以及女性性幼稚症(由于生产受损)引起的性激素。先前已报道了几种导致17α-羟化酶/ 17,20-裂合酶缺乏的CYP17突变。在本研究中,我们描述了两个巴西姐妹的一种新的CYP17突变,这些姐妹患有原发性闭经,46,XY核型,基础水平高的孕酮(3.4-4.9 ng / mL)和近亲父母出生的低钾血症。在对CYP17编码区进行PCR和自动测序后,在患者中发现第5外显子重复了25 bp。根据P450c17的分子模型,该复制起始于密码子318,导致位置320处的终止密码子过早,导致蛋白质无效且被截短。因此,我们扩大了CYP17突变的范围,描述了两个姐妹中该基因中发现的最大重复,并结合了17α-羟化酶/ 17,20-裂合酶缺乏症的临床表型,并强调了P450c 17分子模型预测功能的重要性这些突变的影响。
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