PDF(Pubmed)
Abstract：
The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of non-classical 21-hydroxylase deficiency. For this study, we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature, which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal hyperplasia.
Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins.
We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability.
Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.
Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively analyzed. We examined the effects of gene mutations on protease activity and constructed three-dimensional structure prediction models of proteins.
We describe 10 patients with 11beta-hydroxylase gene mutations (n = 5, 46,XY; n = 5, 46,XX), with 10 novel mutations were reported. Female patients received treatment at an early stage, with an average age of 2.08 ± 1.66 years, whereas male patients received treatment significantly later, at an average age of 9.77 ± 3.62 years. The most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C > T. All mutations lead to spatial conformational changes that affect protein stability.
Our study found that there was no significant correlation between each specific mutation and the severity of clinical manifestations. Different patients with the same gene pathogenic variant may have mild or severe clinical manifestations. The correlation between genotype and phenotype needs further study. Three-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.
摘要：
背景：非经典11β-羟化酶缺乏症的临床表现与非经典21-羟化酶缺乏症的临床表现非常相似。对于这项研究，我们研究了11β-羟化酶缺乏症引起的先天性肾上腺增生的临床和分子特征之间的关系，并复习了相关文献，有望为先天性肾上腺增生症的临床诊断和分析提供帮助。
方法：回顾性分析2018-2022年我院收治的10例先天性肾上腺增生患者的临床资料。我们研究了基因突变对蛋白酶活性的影响，并构建了蛋白质的三维结构预测模型。
结果：我们描述了10例11β-羟化酶基因突变的患者（n=5，46，XY；n=5，46，XX），报告了10个新突变。女性患者在早期接受治疗，平均年龄为2.08±1.66岁，而男性患者接受治疗的时间明显较晚，平均年龄为9.77±3.62岁。发现中国人群中最常见的CYP11B1致病性变异为c.136C>T。所有突变均导致影响蛋白质稳定性的空间构象变化。
结论：我们的研究发现，每个特定突变与临床表现的严重程度之间没有显着相关性。具有相同致病基因变异的不同患者可有轻度或重度临床表现。基因型与表型之间的相关性有待进一步研究。三维蛋白质模拟可以为基因突变的病理生理学机制提供额外的支持。
方法：回顾性分析2018-2022年我院收治的10例先天性肾上腺增生患者的临床资料。我们研究了基因突变对蛋白酶活性的影响，并构建了蛋白质的三维结构预测模型。
结果：我们描述了10例11β-羟化酶基因突变的患者（n=5，46，XY；n=5，46，XX），报告了10个新突变。女性患者在早期接受治疗，平均年龄为2.08±1.66岁，而男性患者接受治疗的时间明显较晚，平均年龄为9.77±3.62岁。发现中国人群中最常见的CYP11B1致病性变异为c.136C>T。所有突变均导致影响蛋白质稳定性的空间构象变化。
结论：我们的研究发现，每个特定突变与临床表现的严重程度之间没有显着相关性。具有相同致病基因变异的不同患者可有轻度或重度临床表现。基因型与表型之间的相关性有待进一步研究。三维蛋白质模拟可以为基因突变的病理生理学机制提供额外的支持。
