ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : Issue : Year : 2024
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Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Identification of a Novel <i>CYP11B2</i> Variant in a Family with Varying Degrees of Aldosterone Synthase Deficiency [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2024; 16(1): 95-101 | DOI: 10.4274/jcrpe.galenos.2022.2022-3-4

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. Mooij1
1University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children’s Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
2Radboud University Medical Center, Department of Human Genetics, Nijmegen, The Netherlands
3University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
4University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children’s Hospital, Department of Pediatrics, Amsterdam, The Netherlands
5Radboud University Medical Center, Amalia Children’s Hospital, Department of Pediatric Endocrinology, Nijmegen, The Netherlands
6University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Department of Endocrinology, 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 biochemical and genetic work-up performed and describe potential pitfalls in CYP11B2 sequencing due to its homology to CYP11B1.

Keywords: Aldosterone synthase, mineralocorticoid, CYB11B2, hypoaldosteronism

Mark R. Garrelfs, Tuula Rinne, Jacquelien J. Hillebrand, Peter Lauffer, Merijn W. Bijlsma, Hedi L. Claahsen-van der Grinten, Nicole de Leeuw, Martijn J.J. Finken, Joost Rotteveel, Nitash Zwaveling-Soonawala, Max Nieuwdorp, A.S. Paul van Trotsenburg, Christiaan F. Mooij. Identification of a Novel CYP11B2 Variant in a Family with Varying Degrees of Aldosterone Synthase Deficiency. J Clin Res Pediatr Endocrinol. 2024; 16(1): 95-101

Corresponding Author: Mark R. Garrelfs, Netherlands
Manuscript Language: English
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