Clinical Characteristics And Gene Mutation Analysis Of Nephronophthisis

Objective: To summarize the clinical features of nephronophthisis(NPHP),and to analyze the mutations of NPHP related genes in patients and family members to improve the understanding of the disease.Methods: Patients diagnosed with NPHP at the Department of Pediatrics Nephrology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were enrolled.We collected clinical data and summarized their clinical manifestations and imaging characteristics.All the patients were performed next generation sequencing,and the positive ones were verified by sanger sequencing.Results : A total of 15 patients of NPHP were diagnosed within 2 years,11 patients were sporadic,and 4 patients were familial,including 12 boys and 3 girls,aged from 11 monthes to 14 years old.2 patients were consistent with diagnosis of infantile NPHP,13 patients fulfilled the juvenile NPHP.The onset of symptoms is polydipsia,polyuria,fatigue,growth retardation and pale.There were 13 patients of abnormal urine,and 12 patients had progressed to chronic renal failure at the time of treatment.7 patients presented with isolated NPHP,8 patients with extrarenal phenotype,including 1 polydactyly,2 situs inversus,1 congenital heart disease,2 liver abnormalities,3 retinieis pigmentosa.From the result of renal ultrasonography,we can find that 10 patients had small kidney,7 patients had renal cysts,13 patients had increased echogenicity,8 patients had abnormal corticomedullary differentitation.In the 15 patients,10 were found to have pathogenic mutations,3 were NPHP12,accounting for 30%(3/10),and the rest were NPHP1,NPHP5,MKS1,BBS2,IFT122,IFT140,and IFT172.Conclutions : Clinical manifestations of NPHP include growth retardation,anemia,polydipsia,polyuria,renal failure,increased renal echogenicity,abnormal corticomedullary differentitation,cyst formation.Some patients have extrarenal manifestations,such as retinitis pigmentosa,situs inversus,congenital heart diaease,polydactyly,liver fibrosis,etc.There are many NPHP genotypes in this group,except for NPHP12,the rest are relatively few,indicating that NPHP has high genetic heterogeneities.