Premium
Molecular genetic studies in a case series of isolated hypoaldosteronism due to biosynthesis defects or aldosterone resistance
Author(s) -
Turan Ihsan,
Kotan Leman Damla,
Tastan Mehmet,
Gurbuz Fatih,
Topaloglu Ali Kemal,
Yuksel Bilgin
Publication year - 2018
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13603
Subject(s) - aldosterone , hypoaldosteronism , pseudohypoaldosteronism , hyperkalemia , medicine , endocrinology , biology , aldosterone synthase , hyponatremia , mineralocorticoid , genetics , blood pressure , renin–angiotensin system
Summary Background and Aim Hypoaldosteronism is associated with either insufficient aldosterone production or aldosterone resistance (pseudohypoaldosteronism). Patients with aldosterone defects typically present with similar symptoms and findings, which include failure to thrive, vomiting, hyponatremia, hyperkalemia and metabolic acidosis. Accurate diagnosis of these clinical conditions therefore can be challenging. Molecular genetic analyses can help to greatly clarify this complexity. The aim of this study was to obtain an overview of the clinical and genetic characteristics of patients with aldosterone defects due to biosynthesis defects or aldosterone resistance. Design and Patients We investigated the clinical and molecular genetic features of 8 consecutive patients with a clinical picture of aldosterone defects seen in our clinics during the period of May 2015 through October 2017. We screened CYP 11B2 for aldosterone synthesis defects and NR 3C2 and the three EnaC subunits ( SCNN 1A, SCNN 1B and SCNN 1G ) for aldosterone resistance. Results We found 4 novel and 2 previously reported mutations in the genes CYP 11B2, NR 3C2, SCNN 1A and SCNN 1G in 9 affected individuals from 7 unrelated families. Conclusion Molecular genetic investigations can help confidently diagnose these conditions and clarify the pathogenicity of aldosterone defects. This study may expand the clinical and genetic correlations of defects in aldosterone synthesis or resistance.