Identification of a Novel CYP11B2 Variant in a Family with Varying Degrees of Aldosterone Synthase Deficiency
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
Affiliations
Mark R. Garrelfs
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Tuula Rinne
Radboud University Medical Center, Department of Human Genetics, Nijmegen, The Netherlands
Jacquelien J. Hillebrand
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Peter Lauffer
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Merijn W. Bijlsma
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatrics, Amsterdam, The Netherlands
Hedi L. Claahsen-van der Grinten
Radboud University Medical Center, Amalia Children's Hospital, Department of Pediatric Endocrinology, Nijmegen, The Netherlands
Nicole de Leeuw
Radboud University Medical Center, Department of Human Genetics, Nijmegen, The Netherlands
Martijn J.J. Finken
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Joost Rotteveel
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Nitash Zwaveling-Soonawala
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Max Nieuwdorp
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Department of Endocrinology, Amsterdam, The Netherlands
A.S. Paul van Trotsenburg
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric Endocrinology, Amsterdam, The Netherlands
Christiaan F. Mooij
University of Amsterdam and Vrije Universiteit, Amsterdam University Medical Centers, Emma Children's Hospital, Department of Pediatric 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.
