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Research Article

X连锁阿尔波特综合征的汉族家庭中的COL4A5错义变体。

卷 19, 期 10, 2019

页: [758 - 765] 页: 8

弟呕挨: 10.2174/1566524019666190906144214

价格: $65

摘要

背景：Alport综合征（AS）是一种遗传性家族性肾病，其特征是进行性血尿性肾炎，双侧感觉神经性听觉不全和眼部异常。 X连锁AS（XLAS）是主要的AS形式，在临床上是异质的，它与IV型胶原蛋白α5链基因（COL4A5）的缺陷有关。 目的：本研究的目的是在3代汉族谱系中发现导致肾脏疾病的遗传缺陷。 方法：收集并记录详细的家族史和家庭成员的临床资料。在先证者中应用了全外显子组测序（WES）来筛选潜在的遗传变异，然后使用Sanger测序来验证该家族中的变异。招募了200名没有肾脏疾病的种族匹配的正常人（男性/女性：100/100，年龄37.5 ... 5.5岁）作为对照。 结果：三名患者（I：1，II：1和II：2）出现镜下血尿和蛋白尿，I：1患者在55岁时出现尿毒症和终末期肾病（ESRD），并表现出感觉神经性听力丧失。患者II：2出现轻度左耳听力下降。白内障存在于I：1和II：1患者中。已发现位于外显子28的Gly-X-Y重复序列中的COL4A5基因错义变体c.2156G> A（p.G719E）与该家族的肾脏疾病共隔离。该变体在200个种族匹配的对照中不存在。 结论：通过进行WES和Sanger测序，发现COL4A5错义变体c.2156G> A（p.G719E）与肾脏疾病共分离，并且该变体可能是该疾病的遗传原因在这个家庭。我们的研究可能会扩展XLAS的突变谱，可能对该家庭的遗传咨询有用。在以下研究中，有必要进行与遗传缺陷相关的进一步功能研究。

关键词: X连锁Alport综合征，COL4A5基因，IV型胶原蛋白，α3α4α5网络，WES，Sanger测序。

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