Novel Variant in the CNNM2 Gene Associated with Dominant Hypomagnesemia
Fecha
2020-09-30Autor
García Castaño, Alejandro
Antón Gamero, Montserrat
Mejia, Natalia
Ponce, Jenny
Gómez Conde, Sara
Pérez de Nanclares, Gustavo
De la Hoz, Ana Belén
Martínez Salazar, Rosa
Saso Jiménez, Laura
Martínez de la Piscina Martín, Idoia
Urrutia, Inés
Velasco, Olaia
Aguayo Calcena, Aníbal
Gaztambide Sáenz, María Sonia
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Plos One 15(9) : (2020) // Article ID e0239965
Resumen
The maintenance of magnesium (Mg2+) homeostasis is essential for human life. The Cystathionine-beta-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 theCNNM2gene 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.