CNNM2 homozygous mutations cause severe refractory hypomagnesemia, epileptic encephalopathy and brain malformations

European Journal of Medical Genetics
Andrea AccogliValeria Capra

Abstract

Magnesium (Mg2+) plays a crucial role in many biological processes especially in the brain, heart and skeletal muscle. Mg2+ homeostasis is regulated by intestinal absorption and renal reabsorption, involving a combination of different epithelial transport pathways. Mutations in any of these transporters result in hypomagnesemia with variable clinical presentations. Among these, CNNM2 is found along the basolateral membrane of distal tubular segments where it is involved in Mg2+ reabsorption. To date, heterozygous mutations in CNNM2 have been associated with a variable phenotype, ranging from isolated hypomagnesemia to intellectual disability and epilepsy. The only homozygous mutation reported so far, is responsible for hypomagnesemia associated with a severe neurological phenotype characterized by refractory epilepsy, microcephaly, severe global developmental delay and intellectual disability. Here, we report the second homozygous CNNM2 mutation (c.1642G > A,p.Val548Met) in a Moroccan patient, presenting with hypomagnesemia and severe epileptic encephalopathy. Thus, we review and discuss the phenotypic spectrum associated with CNNM2 mutations.

Citations

Oct 1, 2020·PloS One·Alejandro García-CastañoSonia Gaztambide
Dec 18, 2019·International Journal of Molecular Sciences·Paula Giménez-MascarellLuis Alfonso Martínez-Cruz
Jul 1, 2020·Acta Physiologica·Gijs A C FrankenJeroen H F de Baaij
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Dec 23, 2019·Structure·Yu Seby ChenKalle Gehring
Apr 17, 2021·Scientific Reports·Gijs A C FrankenJeroen H F de Baaij
Apr 29, 2021·The Proceedings of the Nutrition Society·Willem BosmanJeroen H F de Baaij
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Nov 17, 2021·Kidney Research and Clinical Practice·Felix Claverie-MartinVictor Garcia-Nieto

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