The NPHS2 gene encodes a protein called podocin, which is crucial in maintaining the structure and function of the glomerular filtration barrier in the kidneys. This gene is located on chromosome 1q25-q31 and plays a significant role in the health of the kidneys.
Mutations in the NPHS2 gene are associated with a condition known as Steroid-Resistant Nephrotic Syndrome (SRNS), a severe kidney disorder that often manifests in early childhood. This condition is characterized by proteinuria, hypoalbuminemia, and edema. Understanding the NPHS2 gene helps in diagnosing and managing SRNS in pediatric patients.
There are several known mutations in the NPHS2 gene that can lead to SRNS. One of the most common mutations is p.R138Q, which appears frequently in patients of European descent. Another notable mutation is p.V290M. Genetic testing can help identify these mutations and confirm a diagnosis.
The diagnosis of SRNS usually involves a combination of clinical evaluation, laboratory tests, and genetic testing. Symptoms such as severe proteinuria and resistance to steroid treatment prompt further investigation. Genetic testing for mutations in the NPHS2 gene can provide definitive evidence of the condition.
Treatment for SRNS caused by mutations in the NPHS2 gene can be challenging. Since the condition is resistant to steroids, other immunosuppressive therapies such as calcineurin inhibitors (e.g., cyclosporine or tacrolimus) are often used. Supportive treatments, including ACE inhibitors or ARBs, can help reduce proteinuria. In severe cases, kidney transplantation may be necessary.
The prognosis for patients with NPHS2-related SRNS varies. Some children may respond well to alternative therapies and maintain stable kidney function for years, while others may progress to chronic kidney disease (CKD) or end-stage renal disease (ESRD), requiring dialysis or transplantation.
Since NPHS2 mutations are inherited in an autosomal recessive manner, siblings of affected children have a 25% chance of being affected if both parents are carriers. Genetic counseling is recommended for families to understand the risks and consider testing for other siblings or future pregnancies.
Future Directions in Research
Ongoing research aims to better understand the mechanisms by which NPHS2 mutations cause SRNS and to develop more effective treatments. Advances in genetic research and personalized medicine hold promise for improving outcomes for affected children.
