Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.
Dent Disease in Chinese Children and Findings from Heterozygous Mothers: Phenotypic Heterogeneity, Fetal Growth, and 10 Novel Mutations.
复制标题
中国儿童的牙病和杂合子母亲的发现：表型异质性、胎儿生长和 10 个新突变
DOI：
10.1016/j.jpeds.2016.04.007
复制
发表时间：
2016-07
期刊：
影响因子：
--
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Li F;Yue Z;Xu T;Chen M;Zhong L;Liu T;Jing X;Deng J;Hu B;Liu Y;Wang H;Lai KN;Sun L;Liu J;Maxwell PH;Wang Y
目的探讨中国儿童及其杂合母亲患登特病的表型特征，并建立遗传诊断方法。使用修改后的方案，我们筛选了1288例蛋白尿患者。来自16个家庭的19名男孩通过存在CLCN5或OCRL1的功能丧失/有害突变被诊断为Dent病。我们还分析了16名患者的母亲，并检查了她们的怀孕记录。我们在15名男孩中检测到14个CLCN5功能缺失/有害突变，在4名男孩中检测到2个OCRL1突变。在19名患者中，16名被误诊为其他疾病，19名患者中有11名接受了不正确或不必要的治疗。除14名母亲中的6名外，所有患者在诊断时均无肾钙质症或肾结石。在14例患Dent病1的患者中，8例胎龄大（bbb90百分位数）；15例中有8例（53.3%）患有佝偻病。我们还预测了4个突变蛋白的结构变化。小儿凹陷病常被误诊；基因检测可以得到正确的诊断。肾钙质沉着症或肾结石可能不是敏感的诊断标准。我们在CLCN5和OCRL1中发现了10个新的突变。本文讨论了CLCN5功能改变可能影响胎儿生长的可能性，以及佝偻病高发率与低钙摄入之间的可能联系。
To characterize the phenotypes of Dent disease in Chinese children and their heterozygous mothers and to establish genetic diagnoses. Using a modified protocol, we screened 1288 individuals with proteinuria. A diagnosis of Dent disease was established in 19 boys from 16 families by the presence of loss of function/deleterious mutations in CLCN5 or OCRL1. We also analyzed 16 available patients’ mothers and examined their pregnancy records. We detected 14 loss of function/deleterious mutations of CLCN5 in 15 boys and 2 mutations of OCRL1 in 4 boys. Of the patients, 16 of 19 had been wrongly diagnosed with other diseases and 11 of 19 had incorrect or unnecessary treatment. None of the patients, but 6 of 14 mothers, had nephrocalcinosis or nephrolithiasis at diagnosis. Of the patients, 8 of 14 with Dent disease 1 were large for gestational age (>90th percentile); 8 of 15 (53.3%) had rickets. We also present predicted structural changes for 4 mutant proteins. Pediatric Dent disease often is misdiagnosed; genetic testing achieves a correct diagnosis. Nephrocalcinosis or nephrolithiasis may not be sensitive diagnostic criteria. We identified 10 novel mutations in CLCN5 and OCRL1. The possibility that altered CLCN5 function could affect fetal growth and a possible link between a high rate of rickets and low calcium intake are discussed.
登录
查看更多内容
影响因子：
--
作者：
Shrimpton, Antony E.;Hoopes, Richard R., Jr.;Scheinman, Steven J.
通讯作者：
Scheinman, Steven J.
影响因子：
2.3
作者：
Dietz, Patricia M.;Rizzo, Joanne H.;Hornbrook, Mark C.
通讯作者：
Hornbrook, Mark C.
影响因子：
3.9
作者：
Mansour-Hendili, Lamisse;Blanchard, Anne;Vargas-Poussou, Rosa
通讯作者：
Vargas-Poussou, Rosa
影响因子：
19.6
作者：
Nakazato, H;Yoshimuta, J;Hattori, S
通讯作者：
Hattori, S
影响因子：
64.8
作者：
Piwon, N;Günther, W;Jentsch, TJ
通讯作者：
Jentsch, TJ