Abstract: AbstractObjective：To summarize and review the clinical data of two children with juvenile nephronophthisis so as to improve its knowledge.Methods：Clinical data of two cases with juvenile nephronophthisis were summarized, including clinical manifestations, laboratory findings, renal pathological changes and imaging data. This study used next generation sequencing to screen 4 000 genes. Significant variants detected by next generation sequencing were confirmed by conventional Sanger sequencing and segregation analysis was performed using parental DNA samples.Results：Two cases were both male. The age of onset was 3 months and 17 months respectively. The symptoms of jaundice and liver dysfunction were the first symptoms, 2 cases all progressed to ESRD, at the age of 11 and 35 months respectively. 1 case of renal biopsy showed that renal tubulointerstitial inflammation, mild glomerular mesangial proliferation, segmental endothelial cell proliferation, in line with the renal tubules, the change of small lesion, no cyst; liver biopsy showed liver cell diffuse degeneration, interstitial fibrosis, regional bile duct hyperplasia, inflammatory cells infiltration. Family surveys did not identify members with similar diseases. In case 1, there were heterozygous missense mutations in the NPHP3 gene C.2369A>G (p.L790P) and c.1358A>G (p.L453P), and in 2 cases there were c.1174C>T (p.R392X) nonsense mutations and IVS263A>G shear mutations. Family mutation analysis revealed that the above mutations were derived from their parents, and they were complex heterozygous mutations. None of the above mutations was found in 100 normal controls. Both p.L453P and p.L790P missense mutations were predicted to be deleterious mutations by online software PolyPhen and SIFT, and IVS263A>G shear mutations were also predicted to be deleterious mutations by the online software MaxEntScan. None of the above mutations had previously been reported. High throughput sequencing revealed no mutations causing other diseases. A review of the literature found that a total of 18 articles (Chinese 1 article) met the inclusion criteria, in these reported 1 504 cases of sporadic and familial NPNP patients by NPHP3 gene sequencing, NPHP3 gene were found in 79 cases with homozygous or compound heterozygous mutations. Of these 79 cases of patients with NPHP3 mutation, 19 cases in the neonatal period had progressed to ESRD, and needed renal replacement therapy, were often associated with lung hypoplasia, pancreatic cyst, these patients showed less fetal amniotic fluid, bilateral renal enlargement by ultrasound and cystic change. They were usually diagnosed as autosomal recessive polycystic kidney disease. 20 cases (including 2 cases of this study) progressed to ESRD before the age of 5, with abnormal liver function, anemia was the main manifestation, often accompanied by liver fibrosis and bile duct dysplasia. The other 42 cases progressed to ESRD after the age of 5 showed anemia, renal dysfunction, hypertension and renal phenotype. Conclusion： NPHP caused by mutations in NPHP3 gene is not juvenile nephronophthisis in the traditional sense, because NPHP3 patients can progress to endstage renal disease at any age. If infant and early child present with unknown jaundice and abnormal liver function, which may be caused by mutations in NPHP3 gene. c.1358A>G, C.2369A>G and c.1174C>T mutations are novel mutations in this study, they may further expand the NPHP3 gene mutation spectrum.