A Novel Homozygous Pathogenic Variant in Cyp11b1 in a Female Iranian Patient With 11B Hydroxylase Deficiency Publisher



Hoseinzadeh M¹ ; Molavi N¹ ; Norouzi M¹ ; Aghaei S² ; Zeinalian M¹ ; Hashemipour M³ ; Tabatabaiefar MA^{1, 4, 5} Show Affiliations
Source: Lab Medicine Published:2023

Abstract

Objective: Congenital adrenal hyperplasia (CAH) addresses a number of autosomal recessive disorders characterized by the enzyme defects in steroid hormones biosynthesis. The second common form of CAH is caused by mutations in the CYP11B1 gene. Here, we reveal a novel mutation in the CYP11B1 gene related to the 11βOHD phenotype. Methods and Results: Sequence analysis of the CYP11B1 gene in a 19-year-old Iranian woman with the 11βOHD phenotype was performed. In silico analysis and molecular docking were done. A novel missense homozygous variant c.1351C > T (p.L451F) in the CYP11B1 gene was identified in the patient and, according to American College of Medical Genetics and Genomics criteria, was categorized as likely pathogenic. Protein docking showed destructive effects of the variant on the CYP11B1 protein-ligand interactions. Conclusion: This study broadens the CYP11B1 mutation spectrum and introduces the novel p.L451F likely pathogenic variant leading to destructive effects on protein-ligand interactions. Our results provide reliable information for genetic counseling and molecular diagnostics of CAH. © 2022 The Author(s).