Congenital Nephrotic Syndrome

Congenital nephrotic syndrome only makes up between 2-8% of all forms of nephrotic syndrome, but is a hot topic in that there are numerous genes continuously being identified which are helping to advance our understanding of podocyte biology.

A list of nephrotic syndrome-causing genes identified thus far with a brief description of each is listed below:

1. nephrin (NPHS1): this was the first gene identified which causes congenital nephrotic syndrome of the Finnish type. As shown in the cartoon above, nephrin is a major component of the slit diaphragm.

2. podocin (NPHS2): this was the next gene identified and is the most commonly mutated gene causing steroid-resistant nephrotic syndrome.

3. WT1: this is the Wilms Tumor gene which acts as a transcriptional activator or repressor and is essential for proper development of the genitourinary system.

4. LAMB2: this is a gene for laminin, one of the components of the glomerular basement membrane.

5. PLCE1: this surprising gene--which unlike the others does not play an important structural role in the slit diaphragm--encodes an isoform of phospholipase epsilon gene. Individuals with this mutation actually show an increased responsiveness towards steroid therapy.

6. alpha-actinin-4: this gene encodes an actin filament-crosslinking protein which can cause congenital FSGS.

7. TRPC6: this gene encodes a calcium channel expressed in podocytes, and mutations in it can result in congenital FSGS.

This list of genes causing congenital nephrotic syndrome is likely to expand as there are families with this condition which do not link to any of the above loci.