To explore the approaches and diagnostic yield of genetic testing for renal disease in children, we describe the genotype and phenotype of the national cohort of children with renal disease from 13 different regions of China recruited from 2014 to 2018 by building up the multicenter registration system (Chinese Children Genetic Kidney Disease Database, CCGKDD). Genetic diagnosis was confirmed in 42.1% of our cohort of 1001 pediatric patients with clinical suspicion of a genetic renal disease. Of the 106 distinct monogenetic disorders detected, 15 accounted for 60.7% of genetic diagnoses. The diagnostic yield was 29.1% in steroid resistant nephritic syndrome (SRNS), 61.4% in cystic renal disease, 17.0% in congenital anomalies of the kidney and urinary tract (CAKUT), 62.3% in renal tubular disease/renal calcinosis, and 23.9% for chronic kidney disease (CKD) 3 to 5 stage with unknown origin. Genetic approaches of target gene sequence (TGS), singleton whole‐exome sequencing (WES) and trio‐WES were performed with diagnostic rates of 44.8%, 36.2%, and 42.6%, respectively. The early use of trio‐WES could improve the diagnostic rate especially in renal tubular disease and calcinosis. We report the genetic spectrum of Chinese children with renal disease. Establishment of the CCGKDD will improve the genetic work on renal disease.

WHAT'S KNOWN ON THIS SUBJECT:The sensitivities of 99m Tcdimercaptosuccinic acid in predicting vesicoureteral reflux reported by different institutions were at different levels for young children with acute febrile urinary tract infection. Tc-dimercaptosuccinic acid (DMSA) scan in predicting dilating vesicoureteral reflux (VUR) among young children with a febrile urinary tract infection (UTI). WHAT THIS STUDY ADDS: METHODS:The medical records of children (#2 years of age), presenting with febrile UTI between January 2000 and December 2011, were retrospectively reviewed. RESULTS:A total of 523 children were included in this study, of whom 397 children (75.9%) had abnormal DMSA results and 178 children (34.0%) were identified as VUR on micturating cystourethrography (MCU). Among all the patients, the number of children with dilating VUR was 151 (28.9%). The rate of abnormal results on DMSA for the dilating VUR group was significantly higher than the rates for the non-VUR and low-grade VUR groups (P , .01). In the ,6 months age group and $6 months age group, the sensitivities of DMSA in predicting dilating VUR were 96.15% and 100.0%, respectively, the negative predictive values were 97.26% and 100.0%, respectively, and the negative likelihood ratios were 0.0911 and 0.0000, respectively. CONCLUSION: For children #2 years of age with a febrile UTI, an acute DMSA scan is valuable in the exclusion of dilating VUR. The likelihood of the presence of dilating VUR on MCU is rather low when the result of DMSA is negative. DMSA should be conducted to assess the need for an MCU. Pediatrics 2014;133:e30-e38 AUTHORS:

Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci (HNF1B, PAX2, EYA1, etc.), the genetic etiology of CAKUT remains to be elucidated for most patients. In this study, we report that disruption of the Holliday Junction resolvase gene Gen1 leads to renal agenesis, duplex kidney, hydronephrosis, and vesicoureteral reflux (VUR) in mice. GEN1 interacts with SIX1 and enhances the transcriptional activity of SIX1/EYA1, a key regulatory complex of the GDNF morphogen. Gen1 mutation impairs Grem1 and Gdnf expression, resulting in excessive ureteric bud formation and defective ureteric bud branching during early kidney development. These results revealed an unidentified role of GEN1 in kidney development and suggested its contribution to CAKUT.

Short term and local application of DHT at low doses in patients with micropenis could accelerate penile growth effectively without evident side effects; however, precautions still need be taken due to the paucity of long term study and the lack of ideal DHT dosage.

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