1. The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone
- Author
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Ioannis Petrakis, Eleni Drosataki, Ioanna Stavrakaki, Kleio Dermitzaki, Dimitra Lygerou, Myrto Konidaki, Christos Pleros, Nikolaos Kroustalakis, Sevasti Maragkou, Ariadni Androvitsanea, Ioannis Stylianou, Ioannis Zaganas, and Kostas Stylianou
- Subjects
Inorganic Chemistry ,Amino Acid Substitution ,Organic Chemistry ,Magnesium ,General Medicine ,Physical and Theoretical Chemistry ,Spironolactone ,Kidney ,Molecular Biology ,Cation Transport Proteins ,Spectroscopy ,Catalysis ,Computer Science Applications - Abstract
Renal hypomagnesemia syndromes involving CNNM2 protein pathogenic variants are associated with variable degrees of neurocognitive dysfunction and hypomagnesemia. Here, we report a family with a novel CNNM2 p.Pro482Ala variant, presenting with overt hypomagnesemia and mild neurological involvement (autosomal dominant renal hypomagnesemia 6, HOMG6, MIM# 613882). Using a bioinformatics approach, we showed that the p.Pro482Ala amino acid substitution causes a 3D conformational change in CNNM2 structure in the cystathionin beta synthase (CBS) domain and the carboxy-terminal protein segment. A novel finding was that aldosterone inhibition with spironolactone helped to alleviate hypomagnesemia and symptoms in the proband.
- Published
- 2022