Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome
Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome
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DOI：
10.2215/cjn.05670517
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发表时间：
2018-02-07
影响因子：
9.8
通讯作者：
Vargas-Poussou, Rosa
中科院分区：
文献类型：
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作者：
Legrand, Anne;Treard, Cyrielle;Vargas-Poussou, Rosa
背景与目的位于X染色体上的MAGED2基因突变最近在患有一过性Bartter综合征或特发性羊水过多的男性中被检测到。这项研究的目的是分析该基因突变的人群在法国产前巴特综合征患者队列中的比例。设计、设置、参与者和测量法国产前巴特综合征患者队列包括171个家庭。在75%的病例中发现了与1-4型病毒有关的基因突变。在遗传原因不明的患者(n=42)中，报告了12例一过性产前巴特综合征。结果16个家系共17例MAGED2基因发生突变，其中12例为一过性产前巴特综合征。检测到15种不同的突变(1种完全缺失、3种移码、3种剪接、3种无义、2种基础缺失和3种错义)；其中13种以前从未被描述过。有趣的是，有两名患者是女性；在其中一名患者中，我们的数据与解释严重程度的X染色体选择性失活一致。结论MAGED2突变可解释法国队列中9%的产前Bartter综合征病例，占无其他特征突变患者的38%，占阴性病例男性先证者的44%。我们的研究证实了之前发表的数据，并表明女性可能会受到影响。因此，该基因必须包括在最严重的巴特综合征临床形式的筛查中。
Background and objectives Mutations in the MAGED2 gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome.Design, setting, participants, & measurements The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause (n=42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the MAGED2 gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases.Results We detected mutations in MAGED2 in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases.Conclusions MAGED2 mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome.