The impact of the clinical CYP11B2 mutation V386A strongly depends on the enzyme&amp;rsquo;s genetic background

Context Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting and failure to thrive. The main causes of this rare autosomal recessive disorder are pathogenic variants of the CYP11B2 gene leading to Aldosterone Synthase Deficiency. Objective To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical and hormonal profile suggestive of Aldosterone Synthase Deficiency. Design Clinical and molecular study. Setting Tertiary Academic Children’s Hospital, Center for Rare Pediatric Endocrine Diseases. Patients and Methods Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out in order to evaluate protein stability and potential pathogenicity. Results CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, six of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The six novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C and the donor splice site variant of intron 8, c.1398 + 1G>A. Conclusion Molecular diagnosis was achieved in 62 patients with Aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

The impact of the clinical CYP11B2 mutation V386A strongly depends on the enzyme’s genetic background

Cited by 2 publications

References 13 publications

Underestimated reactions and regulation patterns of adrenal cytochromes P450

Underestimated reactions and regulation patterns of adrenal cytochromes P450

Molecular Analysis of the CYP11B2 Gene in 62 Patients with Hypoaldosteronism Due to Aldosterone Synthase Deficiency

Contact Info

Product

Resources

About