Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
Department of Medicine, Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada.
Am J Med Genet C Semin Med Genet. 2022 Sep;190(3):325-343. doi: 10.1002/ajmg.c.32006. Epub 2022 Oct 8.
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is a developmental disorder of the kidney and/or genito-urinary tract that results in end stage kidney disease (ESKD) in up to 50% of children. Despite the congenital nature of the disease, CAKUT accounts for almost 10% of adult onset ESKD. Multiple lines of evidence suggest that CAKUT is a Mendelian disorder, including the observation of familial clustering of CAKUT. Pathogenesis in CAKUT is embryonic in origin, with disturbances of kidney and urinary tract development resulting in a heterogeneous range of disease phenotypes. Despite polygenic and environmental factors being implicated, a significant proportion of CAKUT is monogenic in origin, with studies demonstrating single gene defects in 10%-20% of patients with CAKUT. Here, we review monogenic disease causation with emphasis on the etiological role of gene developmental pathways in CAKUT.
先天性肾和尿路异常（CAKUT）是一种肾脏和/或泌尿生殖系统的发育障碍，导致多达 50%的儿童发展为终末期肾病（ESKD）。尽管这种疾病是先天性的，但 CAKUT 占成人发病 ESKD 的近 10%。多项证据表明 CAKUT 是一种孟德尔疾病，包括 CAKUT 的家族聚集观察。CAKUT 的发病机制源于胚胎期，肾脏和泌尿道发育的紊乱导致疾病表型的广泛异质性。尽管多基因和环境因素被牵涉其中，但 CAKUT 的很大一部分是单基因起源的，研究表明，10%-20%的 CAKUT 患者存在单个基因缺陷。在这里，我们重点回顾单基因疾病的病因，强调基因发育途径在 CAKUT 中的病因作用。
