Moreover, combined gene defects in more than one podocyte gene may play a role in the development of NS, for example, mutations in both NPHS1 and NPHS2 can cause a tri-allelic hit modifying phenotype (37), and bi-allelic trans-heterozygosity has been described for CD2AP and NPHS2 in sporadic NS (38). Here, NPHS2 is linked to Netherton syndrome.