Compound heterozygous mutations in NPHP4 gene identified in a patient with nephronophthisis and proteinuriaGenetic Testing Reveals New Mutations in Kidney Disease

Nephronophthisis (NPHP), an autosomal recessive kidney disorder characterized by chronic tubulointerstitial nephritis, is the most prevalent monogenic cause of end-stage renal disease (ESRD). Previous studies have identified variants in more than 20 genes, designated NPHP1 to NPHP20, and in additional loci as the genetic causes of NPHP. Here, a Chinese patient who presented with NPHP and proteinuria was enrolled. By employing whole exome sequencing and Sanger sequencing, we identified a rare compound heterozygous mutation in the NPHP4 gene (c.2611C > T/p.R871X and c.2768G > A/p.R923H) in the patient. Sanger sequencing further confirmed that the p.R871X variant was inherited from the father and that the p.R923H variant originated from the mother. Both variants were predicted to be deleterious by bioinformatic software. In accordance with the American College of Medical Genetics and Genomics guideline, the p.R871X variant was classified as pathogenic, and the p.R923H variant was classified as likely pathogenic. So far, neither of these mutations has been reported in patients with NPHP. Our findings contribute to the precise diagnosis of the patient and further underscore the utility of genetic testing in the accurate diagnosis of NPHP.