Editorial: Developmental Disorders of the Kidney and Urinary Tract: Recent Insights From Clinical and Molecular Studies

Frontiers in Pediatrics

article

Eduardo A. Oliveira¹  Robert H. Mak²  Ana Cristina Simões e Silva¹ 

[1] Pediatric Nephrology Unit, Department of Pediatrics, Federal University of Minas Gerais;Division of Pediatric Nephrology, Rady Children's Hospital San Diego, University of California, United States;National Institute of Science and Technology (INCT) of Molecular Medicine

关键词: congenital anomalies of the kidney and urinary tract;    chronic kidney disease;    prenatal diagnosis;    fetal hydronephrosis;    renal hypodysplasia;    genetics;    molecular mechanisms;    gene polymorphism;   

DOI  :  10.3389/fped.2020.00348

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Outstanding advances have been obtained in basic and clinical research on congenital anomalies of the kidney and urinary tract (CAKUT) over the past decade. From the molecular point of view, new generation sequencing has made crucial contributions to our understanding of the biology and pathophysiology of disrupted renal development, including the identification of associated genes and insights into the cellular pathophysiology (1, 2). Approximately 40 different monogenic causes for human CAKUT have so far been identified. Nevertheless, at present only about 20% of CAKUT cases can be explained by these established monogenic causes (3–5). Therefore, it is probably that several additional monogenic causes of human CAKUT have yet to be identified. In this Research Topic, Woolf et al. have demonstrated several rare diseases among the CAKUT complex with defined genetic causes. These studies are indicating that the implicated genes encode smooth muscle, neural or urothelial molecules, or master transcription factors that regulate their expression. However, variants in these same genes do not appear to explain the more common human non-syndromic urinary tract malformations such as primary vesicoureteral reflux. Of note, studies with whole exome sequencing, a technology that seeks variants in the protein coding regions of all genes, is being applied to seek likely pathogenic mutation in clinical cohorts of children born with a range of kidney malformations (6). Such researches have yielded useful genetic information in 10–14% of cases tested (Woolf et al.). Taroni et al. reported, on this Research topic, a case of a 2 years old child with Hypotonia-Cystinuria syndrome (HCS). HCS is a rare disease, caused by a mutation in two contiguous genes (SLC3A1 and PREPL), localized on chromosome 2p21, and it is characterized by both renal involvement with cystine stones and nervous involvement with hypotonia. Interestingly, the case reported had HCS associated with other clinical features of CAKUT, primary obstructed megaureter (POM), cryptorchidism and cardiac involvement. Some clinical features showed in this case report, like cryptorchidism and POM, have never been reported before in patients with HCS.

【 授权许可】

CC BY