Novel variant in the CNNM2 gene associated with dominant hypomagnesemia #MMPMID32997713
Garcia-Castano A; Madariaga L; Anton-Gamero M; Mejia N; Ponce J; Gomez-Conde S; Perez de Nanclares G; De la Hoz AB; Martinez R; Saso L; Martinez de LaPiscina I; Urrutia I; Velasco O; Aguayo A; Castano L; Gaztambide S
PLoS One 2020[]; 15 (9): e0239965 PMID32997713show ga
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 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.
|Adolescent[MESH]
|Adult[MESH]
|Cation Transport Proteins/chemistry/*genetics[MESH]
free
free
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PLoS+One 2020 ; 15 (9): e0239965
