The p.Pro482Ala Variant in the CNNM2 Gene Causes Severe Hypomagnesemia Amenable to Treatment with Spironolactone.

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.

SUBMITTER: Petrakis I 

PROVIDER: S-EPMC9266752 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature