Manna Zhang1, Yanling Liu, Shouyue Sun, Huijie Zhang, Weiqing Wang, Guang Ning, Xiaoying Li. 1. Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Key Laboratory of Endocrine Tumor, Shanghai Institute of Endocrinology and Metabolism, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, 197 RuiJin 2nd Road, Shanghai 200025, China.
Abstract
UNLABELLED: 11β-Hydroxylase deficiency (11β-OHD), caused by CYP11B1 mutations, is characterized by hyporeninemic, hypokalemic hypertension and hyperandrogenism. We identified a prevalent and three novel mutations of CYP11B1 gene in nine patients with classic 11β-OHD. SUBJECTS AND METHODS: Nine patients with 11β-OHD from unrelated families were recruited. The complications of 11β-OHD occurred in three patients who never received glucocorticoid treatment. CYP11B1 gene was sequenced and 11β-hydroxylase enzymatic activities were assessed in vitro. A haplotype analysis was performed to determine a common ancestor for those subjects who carried the same p.R454C mutation. RESULTS: CYP11B1 gene mutations were identified in all patients, with a prevalent (p.R454C) and three novel mutations (p.V148G, IVS7-9C>A, c.1359_1360insG). The p.R141X, p.V148G, c.1359_1360insG and p.R454C mutations retained 4.9%, 3.9%, 3.7%, 4.5% of residual enzymatic activity, respectively. Five of nine patients carried p.R454C mutation, which was only reported in Chinese 11OHD patients. Haplotype analysis showed that this mutation might be inherited from a common ancestor. CONCLUSION: The enzymatic activities for p.R141X, p.V148G, c.1359_1360insG and p.R454C mutants were almost completely abolished, which corresponds to classic form of 11β-OHD. The observations of a prevalent mutation and three novel mutations might have potential clinical utility for genetic counseling and prenatal diagnosis in Chinese 11β-OHD patients.
UNLABELLED: 11β-Hydroxylase deficiency (11β-OHD), caused by CYP11B1 mutations, is characterized by hyporeninemic, hypokalemic hypertension and hyperandrogenism. We identified a prevalent and three novel mutations of CYP11B1 gene in nine patients with classic 11β-OHD. SUBJECTS AND METHODS: Nine patients with 11β-OHD from unrelated families were recruited. The complications of 11β-OHD occurred in three patients who never received glucocorticoid treatment. CYP11B1 gene was sequenced and 11β-hydroxylase enzymatic activities were assessed in vitro. A haplotype analysis was performed to determine a common ancestor for those subjects who carried the same p.R454C mutation. RESULTS:CYP11B1 gene mutations were identified in all patients, with a prevalent (p.R454C) and three novel mutations (p.V148G, IVS7-9C>A, c.1359_1360insG). The p.R141X, p.V148G, c.1359_1360insG and p.R454C mutations retained 4.9%, 3.9%, 3.7%, 4.5% of residual enzymatic activity, respectively. Five of nine patients carried p.R454C mutation, which was only reported in Chinese 11OHD patients. Haplotype analysis showed that this mutation might be inherited from a common ancestor. CONCLUSION: The enzymatic activities for p.R141X, p.V148G, c.1359_1360insG and p.R454C mutants were almost completely abolished, which corresponds to classic form of 11β-OHD. The observations of a prevalent mutation and three novel mutations might have potential clinical utility for genetic counseling and prenatal diagnosis in Chinese 11β-OHD patients.
Authors: Erik van der Wal; Atze J Bergsma; Joon M Pijnenburg; Ans T van der Ploeg; W W M Pim Pijnappel Journal: Mol Ther Nucleic Acids Date: 2017-03-14