Novel variant in the CNNM2 gene associated with dominant hypomagnesemia

García-Castaño A.; Madariaga L.; Antón-Gamero M.; Mejia N.; Ponce J.; Gómez-Conde S.; de Nanclares G.P.; de la Hoz A.B.; Martínez R.; Saso L.; de LaPiscina I.M.; Urrutia I.; Velasco O.; Aguayo A.; Castaño L.; Gaztambide S. · PLoS ONE (2020) · DOI: 10.1371/journal.pone.0239965

Resumen

The maintenance of magnesium (Mg2+) homeostasis is essential for human life. The Cystathionine-β-synthase (CBS)-pair domain divalent metal cation transport mediators (CNNMs) have been described to be involved in maintaining Mg2+ homeostasis. Among these CNNMs, CNNM2 is expressed in the basolateral membrane of the kidney tubules where it is involved in Mg2+ reabsorption. A total of four patients, two of them with a suspected disorder of calcium metabolism, and two patients with a clinical diagnosis of primary tubulopathy were screened for mutations by Next-Generation Sequencing (NGS). We found one novel likely pathogenic variant in the heterozygous state (c.2384C>A; p.(Ser795*)) in the CNNM2 gene in a family with a suspected disorder of calcium metabolism. In this family, hypomagnesemia was indirectly discovered. Moreover, we observed three novel variants of uncertain significance in heterozygous state in the other three patients (c.557G>C; p. (Ser186Thr), c.778A>T; p.(Ile260Phe), and c.1003G>A; p.(Asp335Asn)). Our study shows the utility of Next-Generation Sequencing in unravelling the genetic origin of rare diseases. In clinical practice, serum Mg2+ should be determined in calcium and PTH-related disorders.