Ahn Yo Han, Lee Chung, Kim Nayoung K D, Park Eujin, Kang Hee Gyung, Ha Il-Soo, Park Woong-Yang, Cheong Hae Il
Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Pediatrics, Seoul National University Children's Hospital, Seoul 03080, Korea.
J Clin Med. 2020 Mar 10;9(3):751. doi: 10.3390/jcm9030751.
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. The search for genetic causes of CAKUT has led to genetic diagnosis in approximately 5-20 % of CAKUT patients from Western countries. In this study, genetic causes of CAKUT in Korean children were sought using targeted exome sequencing (TES) of 60 genes reported to cause CAKUT in human or murine models. We identified genetic causes in 13.8% of the 94 recruited patients. Pathogenic single nucleotide variants of five known disease-causing genes, , , , , and were found in 7 cases. Pathogenic copy number variations of 6 patients were found in , , and . Genetic abnormality types did not significantly differ according to CAKUT phenotypes. Patients with pathogenic variants of targeted genes had syndromic features more frequently than those without ( < 0.001). This is the first genetic analysis study of Korean patients with CAKUT. Only one-seventh of patients were found to have pathogenic mutations in known CAKUT-related genes, indicating that there are more CAKUT-causing genes or environmental factors to discover.
先天性肾脏和尿路畸形（CAKUT）是儿童慢性肾脏病最常见的病因。对CAKUT遗传病因的探寻已使西方国家约5%-20%的CAKUT患者得到基因诊断。在本研究中，我们采用对60个在人类或小鼠模型中报道可致CAKUT的基因进行靶向外显子组测序（TES）的方法，来寻找韩国儿童CAKUT的遗传病因。我们在94例纳入研究的患者中，有13.8%找到了遗传病因。在7例患者中发现了5个已知致病基因（此处原文缺失基因名称）的致病性单核苷酸变异。在6例患者中发现了（此处原文缺失基因名称）的致病性拷贝数变异。遗传异常类型根据CAKUT表型无显著差异。具有靶向基因致病性变异的患者比无变异的患者更常出现综合征特征（P<0.001）。这是韩国CAKUT患者的首次基因分析研究。仅七分之一的患者被发现在已知的CAKUT相关基因中有致病性突变，这表明还有更多导致CAKUT的基因或环境因素有待发现。
