Biocruces Bizkaia Health Research Institute, CIBERDEM, CIBERER, Bizkaia, Spain.
Paediatric Nephrology Department, Biocruces Bizkaia Health Research Institute, Hospital Universitario Cruces, CIBERDEM, CIBERER, University of the Basque Country (UPV-EHU), Bizkaia, Spain.
PLoS One. 2020 Sep 30;15(9):e0239965. doi: 10.1371/journal.pone.0239965. eCollection 2020.
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.
镁 (Mg2+) 稳态的维持对人类生命至关重要。半胱氨酸-β-合酶 (CBS)-对二价金属阳离子转运介质 (CNNMs) 已被描述为参与维持 Mg2+ 稳态。在这些 CNNMs 中，CNNM2 表达在肾脏肾小管的基底外侧膜，在那里它参与 Mg2+ 的重吸收。共有四名患者，其中两名疑似钙代谢紊乱，两名临床诊断为原发性肾小管病，通过下一代测序 (NGS) 筛选突变。我们在一个疑似钙代谢紊乱的家族中发现了 CNNM2 基因杂合状态下的一个新的可能致病性变异（c.2384C>A; p.(Ser795*))。在这个家族中，低镁血症是间接发现的。此外，我们在另外三名患者中观察到三个杂合状态下不确定意义的新变异（c.557G>C; p.(Ser186Thr)，c.778A>T; p.(Ile260Phe)，和 c.1003G>A; p.(Asp335Asn))。我们的研究表明，下一代测序在揭示罕见疾病的遗传起源方面具有实用性。在临床实践中，应在钙和 PTH 相关疾病中确定血清 Mg2+。
