Identification of a Novel CYP11B2 Variant in a Family with Varying Degrees of Aldosterone Synthase Deficiency
Mark R. Garrelfs1, Tuula Rinne2, Jacquelien J. Hillebrand3, Peter Lauffer1, Merijn W. Bijlsma4, Hedi L. Claahsen-van Der Grinten5, Nicole De Leeuw2, Martijn J.J. Finken1, Joost Rotteveel1, Nitash Zwaveling-soonawala1, Max Nieuwdorp6, A.S. Paul van Trotsenburg1, Christiaan F. Mooij11Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands.2Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
3Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands
4Department of Pediatrics, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit, Amsterdam, the Netherlands
5Department of Pediatric Endocrinology, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.
6Department of Endocrinology, Amsterdam University Medical Centers, University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands.
Isolated aldosterone synthase deficiency is a rare autosomal recessive disorder caused by pathogenic variants in CYP11B2, resulting in impaired aldosterone synthesis. We report on a neonate with isolated aldosterone synthase deficiency caused by a novel homozygous CYP11B2 variant Chr8: NM_000498.3: c.400G>A p.(Gly134Arg). The patient presented shortly after birth with severe signs of aldosterone deficiency. Interestingly, segregation analysis revealed that the patient’s asymptomatic father was also homozygous for the CYP11B2 variant. Biochemical evaluation of the father indicated subclinical enzyme impairment, characterized by elevated aldosterone precursors. Apparently, this homozygous variant led to different clinical phenotypes in two affected relatives. In this manuscript we elaborate on the performed biochemical and genetic work-up and describe potential pitfalls of CYP11B2 sequencing due to its homology to CYP11B1.
Keywords: Aldosterone Synthase, Mineralocorticoid, CYB11B2, HypoaldosteronismCorresponding Author: Mark R. Garrelfs, Netherlands
Manuscript Language: English
