Wu Hangdi, Xu Qian, Xie Jingyuan, Ma Jun, Qiao Panpan, Zhang Wen, Yu Haijin, Wang Weiming, Qian Ying, Zhang Qianying, Guo Yiqing, Tang Yonghua, Chen Xiao-Nong, Wang Zhaohui, Chen Nan
Department of Nephrology, Institute of Nephrology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Am J Nephrol. 2017;46(1):55-63. doi: 10.1159/000477590. Epub 2017 Jun 16.
Few genetic studies have focused on unilateral renal agenesis (URA), which is a disorder with insidious clinical manifestations and a tendency to result in renal failure. We aimed to detect pathogenic mutations in nephrogenesis-related genes, which were identified by a literature review conducted among a large cohort of Chinese Han patients with URA.
Totally, 86 unrelated URA patients were included. All URA patients were diagnosed by employing radiological methods. Patients with a solitary kidney owing to nephrectomy or renal atrophy due to secondary factors were excluded. Nine (10.5%) patients had a family history of abnormal nephrogenesis. Fifteen (17.4%) had other malformations in the urogenital system. All coding exons and adjacent intron regions of 25 genes were analyzed using next-generation sequencing and validated by Sanger sequencing and 100 ethnically matched healthy controls.
Ten conserved mutations (9 missense mutations and 1 deletion mutation) were identified in SALL1, EYA1, RET, HNF1B, DSTYK, WNT4, and SIX5. All mutations were novel or rare (frequency <0.1%) in the public databases and absent from the 100 healthy controls. Nine patients carried mutations in candidate genes. Most of the patients carried one single heterozygous mutation, except for 2, who respectively carried compound heterozygous mutations and 2 single heterozygous mutations. In addition, 2 patients shared the same mutation in DSTYK.
A total of 10.5% of our URA cases could be explained by mutations in our candidate genes. The mutations in nephrogenesis-related genes in the Chinese Han patients with URA had a decentralized distribution without any hotspot mutations.
很少有基因研究聚焦于单侧肾发育不全（URA），这是一种临床表现隐匿且有导致肾衰竭倾向的疾病。我们旨在检测肾发生相关基因中的致病突变，这些基因是通过对一大群中国汉族URA患者进行文献综述确定的。
共纳入86例无亲缘关系的URA患者。所有URA患者均采用放射学方法进行诊断。排除因肾切除术导致单肾或因继发因素导致肾萎缩的患者。9例（10.5%）患者有肾发生异常的家族史。15例（17.4%）患者有泌尿生殖系统的其他畸形。使用下一代测序分析25个基因的所有编码外显子和相邻内含子区域，并通过桑格测序和100名种族匹配的健康对照进行验证。
在SALL1、EYA1、RET、HNF1B、DSTYK、WNT4和SIX5中鉴定出10个保守突变（9个错义突变和1个缺失突变）。所有突变在公共数据库中都是新的或罕见的（频率<0.1%），在100名健康对照中未出现。9例患者在候选基因中携带突变。大多数患者携带一个单一的杂合突变，除了2例分别携带复合杂合突变和2个单一杂合突变的患者。此外，2例患者在DSTYK中共享相同的突变。
我们的URA病例中共有10.5%可由候选基因中的突变解释。中国汉族URA患者中肾发生相关基因的突变呈分散分布，没有任何热点突变。
