Novel Variant in the CNNM2 Gene Associated with Dominant Hypomagnesemia

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 basolatera...

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Authors: García Castaño, Alejandro, Madariaga Domínguez, Leire, 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, Castaño González, Luis Antonio, Gaztambide Sáenz, María Sonia
Format: article
Publication Date:2020
Country:España
Institution:Universidad del País Vasco
Repository:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/50215
Online Access:http://hdl.handle.net/10810/50215
Access Level:Open access
Keyword:NA+/MG2+ exchangers
CNNM proteins
magnesium
Description
Summary: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.

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