[Clinical features and gene mutation analysis of 13 Chinese juvenile patients with nephronophthisis].

Objective: To explore the clinical features and pathogenic gene mutation of juvenile nephronophthisis (NPHP) in Chinese patients. Method: Clinical data and blood samples of 27 juvenile NPHP patients from 25 families who were initially clinically diagnosed in six hospitals in Guangdong province were collected. NPHP1 homozygous deletions were detected in all patients. Sequencing of NPHP1 gene was performed when homozygous deletions were not found in patients without eye involvement. In patients with eye involvement, NPHP5 sequencing was carried out initially and subsequently NPHP10 gene and NPHP1 when there were no NPHP5 gene mutation found. Result: Diagnosis was confirmed in 13 patients by renal pathology and (or) gene sequencing, including four boys and nine girls with a median onset age of 8.5(0.1-12.8) years. Seven of the 13 patients had a normal routine urine test and six patients had mild to moderate proteinuria. None had persistent hematuria. The estimated glomerular filtration rate of the 13 patients was (12.7±10.7) ml/(min·1.73 m(2)) at the time of diagnosis. Renal cysts were found in only five patients by iconography. Decreased renal size was observed in nine cases and normal renal size in four patients. Renal pathology was available in five patients, renal cysts formation at the cortical-medullar area, thickening and laying tubular basement membrane, were observed. Two of the thirteen children had eye involvement, one had liver impairment and one had growth retardation. NPHP1 gene defects were detected in seven patients with a mutation rate of 25.9%, and large homozygous deletions were observed in three patients. Four patients had single point mutations, i. e. compound heterozygous mutations (c.13 C>T and c. 1520+ 5 G>A) in one patient; homozygous mutation in three patients, two patients were siblings from the same pedigree harbored c. 1756 C>T and the other one harbored c. 1298delA. NPHP5 gene homozygous mutation was found in one pedigree. The fourteen children without renal pathology and whose genetic tests were negative shared similar clinical features with the thirteen patients whose diagnosis were confirmed by gene mutation and (or) renal pathology. Conclusion: The onset of juvenile NPHP is insidious. Urine and renal iconography changes are mild or negative. The ratio of NPHP1 mutant patient is similar with previous reports, but the proportion of NPHP1 gene homozygous deletions is much lower and all of the NPHP1 gene single point mutations detected in this research were novel, which indicates a genetic discrepancy existed between Chinese NPHP patients and the western ones.