CNNM2 homozygous mutations cause severe refractory hypomagnesemia, epileptic encephalopathy and brain malformations
CNNM2 homozygous mutations cause severe refractory hypomagnesemia, epileptic encephalopathy and brain malformations
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DOI：
10.1016/j.ejmg.2018.07.014
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发表时间：
2019-03-01
影响因子：
1.9
通讯作者：
Capra, Valeria
中科院分区：
文献类型：
--
作者：
Accogli, Andrea;Scala, Marcello;Capra, Valeria
镁（Mg2+）在许多生物过程中起着至关重要的作用，特别是在大脑，心脏和骨骼肌中。Mg2+稳态受肠吸收和肾重吸收调节，涉及不同上皮转运途径的组合。这些转运蛋白中的任何一种突变都会导致低镁血症，并伴有不同的临床表现。其中，CNNM 2被发现沿着远侧小管段的基底外侧膜，在那里它参与Mg 2+的重吸收。迄今为止，CNNM 2的杂合突变与可变表型相关，从孤立的低镁血症到智力残疾和癫痫。迄今为止报道的唯一纯合突变导致与以难治性癫痫、小头畸形、严重全面发育迟缓和智力残疾为特征的严重神经系统表型相关的低镁血症。在这里，我们报告了第二个纯合子CNNM 2突变（c.1642G > A，p.Va1548Met）在摩洛哥的病人，表现为低镁血症和严重的癫痫性脑病。因此，我们回顾和讨论与CNNM 2突变相关的表型谱。
Magnesium (Mg2+) plays a crucial role in many biological processes especially in the brain, heart and skeletal muscle. Mg2+ homeostasis is regulated by intestinal absorption and renal reabsorption, involving a combination of different epithelial transport pathways. Mutations in any of these transporters result in hypomagnesemia with variable clinical presentations. Among these, CNNM2 is found along the basolateral membrane of distal tubular segments where it is involved in Mg2+ reabsorption. To date, heterozygous mutations in CNNM2 have been associated with a variable phenotype, ranging from isolated hypomagnesemia to intellectual disability and epilepsy. The only homozygous mutation reported so far, is responsible for hypomagnesemia associated with a severe neurological phenotype characterized by refractory epilepsy, microcephaly, severe global developmental delay and intellectual disability. Here, we report the second homozygous CNNM2 mutation (c.1642G > A,p.Va1548Met) in a Moroccan patient, presenting with hypomagnesemia and severe epileptic encephalopathy. Thus, we review and discuss the phenotypic spectrum associated with CNNM2 mutations.