García-Castaño, AlejandroMadariaga, LeireAntón-Gamero, MontserratMejia, NataliaPonce, JennyGómez-Conde, SaraPérez de Nanclares, GustavoDe la Hoz, Ana BelénMartínez, RosaSaso, LauraMartínez de LaPiscina, IdoiaUrrutia, InésVelasco, OlaiaAguayo, AníbalCastaño, LuisGaztambide, Sonia2023-02-092023-02-092020-09-30http://hdl.handle.net/10668/16352The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AdolescentAdultCation Transport ProteinsCodon, NonsenseFemaleHeterozygoteHigh-Throughput Nucleotide SequencingHumansInfantMagnesiumMalePolymorphism, Single NucleotideRenal Tubular Transport, Inborn ErrorsSequence Analysis, DNAresearch article32997713open access10.1371/journal.pone.02399651932-6203PMC7527205https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0239965&type=printablehttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527205/pdf