Open AccessNovel variant in the CNNM2 gene associated with dominant hypomagnesemia
Author(s) -
Alejandro García-Castaño,
Leire Madariaga,
Montserrat AntónGamero,
Natalia Mejía,
Jenny Ponce,
Sara GómezConde,
Gustavo Pérez de Nanclares,
Ana Belén de la Hoz,
Rosa Martı́nez,
Laura Saso,
Idoia Martinez de la Piscina,
I. Urrutia,
Olaia Velasco,
Aníbal Aguayo,
Luís Castaño,
Sonia Gaztambide
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0239965
Subject(s) - hypomagnesemia , homeostasis , calcium metabolism , reabsorption , genetics , gene , biology , calcium , chemistry , endocrinology , kidney , medicine , magnesium , organic chemistry
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.