NPHS2 mutation analysis and primary nephrotic syndrome in southern Indians

Nephrotic syndrome is one of the most commonly diagnosed primary kidney diseases and its progressive forms can lead to chronic kidney disease and or end-stage renal disease. Steroid-resistant nephrotic syndrome is defined by resistance to standard steroid therapy and it remains one of the most intractable causes of kidney failure. Mutations in NPHS2, which encodes for podocin, an integral membrane protein of the glomerular epithelial cells (podocytes), represent a frequent cause of steroid-resistant nephrotic syndrome worldwide. This study was aimed at screening for known NPHS2 mutations in Indians with nephrotic syndrome.

We screened a cohort of 484 subjects from the southern Indian population for the presence of four missense mutations G92C, P118L, R138Q and D160G within the NPHS2 gene using tetra primer ARMS PCR.

Our results revealed that these mutations were seen only among the patients (14.02%) and were absent in the controls, suggesting their disease-causing nature. Further categorization revealed that these mutations were together responsible for 18.5% of steroid-resistant cases in our study group. Conversely, the studied mutations were not found in the controls as well as in the patients with steroid-sensitive nephrotic syndrome.

This is the first such report from India. More studies are warranted to establish the frequency of NPHS2 mutations in the Asian-Indian population and such analysis may help in developing mutation(s)-specific therapeutic interventions in the future.