Department of Pediatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Rd, Huangpu District, Shanghai, 200025, China.
Department of Pediatric Genetic and Metabolic Endocrinology, West China Second University Hospital,Sichuan University, No. 20, Section 3, Renmin South Road, Sichuan, 610041, China.
World J Pediatr. 2024 Apr;20(4):422-433. doi: 10.1007/s12519-023-00739-1. Epub 2023 Jul 24.
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.
非典型 11β-羟化酶缺陷的临床表现与非典型 21-羟化酶缺陷非常相似。本研究旨在探讨 11β-羟化酶缺陷导致先天性肾上腺皮质增生的临床与分子特征之间的关系，并复习相关文献，以期为先天性肾上腺皮质增生的临床诊断和分析提供帮助。
回顾性分析 2018 年至 2022 年我院收治的 10 例先天性肾上腺皮质增生症患者的临床资料，检测基因突变对蛋白酶活性的影响，并构建蛋白质三维结构预测模型。
描述了 10 例 11β-羟化酶基因突变患者（n=5，46,XY；n=5，46,XX），报告了 10 种新突变。女性患者早期接受治疗，平均年龄为 2.08±1.66 岁，而男性患者接受治疗的年龄明显较晚，平均年龄为 9.77±3.62 岁。中国人群中最常见的 CYP11B1 致病变异是 c.1360C>T。所有突变导致空间构象改变，影响蛋白质稳定性。
本研究发现，特定突变与临床表现严重程度之间无显著相关性。同一基因致病性变异的不同患者可能表现为轻度或重度临床表现。基因型与表型的相关性需要进一步研究。三维蛋白质模拟可能为基因突变的病理生理机制提供额外支持。
