Abstract

Background: X-linked Adrenal Hypoplasia Congenital (AHC) is a rare genetic disorder of primary adrenal insufficiency, often associated with hypogonadotropic hypogonadism. Mutations within the NR0B1 cause AHC. NR0B1 codes the DAX1 protein, which is necessary for hypothalamic-pituitary-adrenal axis development. Methods: Whole-exome sequencing (WES) has been performed on a family with one affected child diagnosed with AHC. Also, the detected mutation was investigated using bioinformatics tools to predict its effects on the protein product and compare the mutated sequence with close species. Results: Adenosine duplication at the genomic position 1397 (g.13946dupA) and coding DNA at position 1163 (c.1163dupA) was detected in the mother and affected child. Segregation analysis confirmed the hemizygote and heterozygote state for c.1163dupA variant in the affected boy and his mother. Finally, the probable damaging effect with significant alterations in the protein structure was predicted. Conclusion: This study expands the spectrum of NR0B1 pathogenic variants and confirms the utility of whole exosome sequencing in genetic diagnosis, future follow-up, and family counseling. © 2022 Elsevier Inc.