Identification of a pathogenic mutation in a Chinese pedigree with polycystic kidney disease
Identification of a pathogenic mutation in a Chinese pedigree with polycystic kidney disease
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DOI：
10.3892/mmr.2019.9921
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Fu, Songbin
中科院分区：
文献类型：
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作者：
Dong, Kexian;Miao, Huanhuan;Fu, Songbin
多囊肾病 (PKD) 是一种危及生命的遗传性疾病，全球发病率为 1:500-1,000。在 PKD 患者的双侧肾脏中观察到许多逐渐增大的囊肿，导致结构损伤和肾功能丧失。本研究分析了一个患有 PKD 的家庭。对先证者进行全外显子组测序，以检测家族中存在的致病基因。通过巢式聚合酶链式反应扩增家族中直系血亲的候选基因片段，然后进行桑格测序。在 PKD1 中检测到一种新的重复变异 (NM_001009944.2:c.9359dupA:p.Y3120_E3121delinsX) 和一种错义突变 (c.G9022A:p.V3008M)。此外，还分析了数据集中发布的 PKD1 的致病性替换。经过分析和确认，PKD1中多囊蛋白-1、脂氧合酶、毒素结构域内的重复变异NM_001009944.2:c.9359dupA:p.Y3120_E3121delinsX被认为是所检查的常染色体显性PKD家系的致病因素。此外，根据对 PKD1 各个区域内 4,805 个致病性取代的分析，多囊蛋白-1 N 端结构域中错义突变的存在可能在 ADPKD 中表现出高致病性。
Polycystic kidney disease (PKD) is a life-threatening inherited disease with a morbidity of 1:500-1,000 worldwide. Numerous progressively enlarging cysts are observed in the bilateral kidneys of patients with PKD, inducing structural damage and loss of kidney function. The present study analyzed one family with PKD. Whole exome sequencing of the proband was performed to detect the pathogenic gene present in the family. Candidate gene segments for lineal consanguinity in the family were amplified by nest polymerase chain reaction, followed by Sanger sequencing. One novel duplication variant (NM_001009944.2:c.9359dupA:p.Y3120_E3121delinsX) and one missense mutation (c.G9022A:p.V3008M) were detected in PKD1. Additionally, the pathogenic substitutions in PKD1 published from the dataset were analyzed. Following analysis and confirmation, the duplication variant NM_001009944.2:c.9359dupA:p.Y3120_E3121delinsX in PKD1, within the polycystin-1, lipoxygenase, -toxin domain, was considered to be the pathogenic factor in the examined family with autosomal dominant PKD. Additionally, based on the analysis of 4,805 pathogenic substitutions in PKD1 within various regions, the presence of the missense mutation in the N-terminal domain of polycystin-1 may present high pathogenicity in ADPKD.