The aim of the study was to evaluate NPHS1 mutations, its susceptibility to the disease, and their association in children with steroid-resistant NS; mutation frequency of 9% was observed in patients with steroid-resistant NS, of which, six mutations and two single-nucleotide polymorphisms observed in the study population were found to be novel.
Mutations in the <i>NPHS1, NPHS2, LAMB2</i>, and the <i>WT1</i> genes are responsible for causing nephrotic syndrome (NS) in two third of the early onset cases.
Loss of function for crb2b and nphs1 in Danio rerio were previously shown to result in loss of the slit diaphragms of the podocytes, leading to the hypothesis that nephrosis develops from an inability to develop a functional glomerular barrier.
To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1).
The NPHS1 kidneys do not express nephrin, and antibodies against this major glomerular filter protein have been observed in NPHS1 children with recurrent NS.
NPHS2 mutations were the most frequent cause of nephrotic syndrome among both families with congenital nephrotic syndrome (39.1%) and infantile nephrotic syndrome (35.3%), whereas NPHS1 mutations were solely found in patients with congenital onset.
The results demonstrate that NPHS1 and NPHS2 mutations are also present in Chinese sporadic NS patients, suggesting that genetic changes of nephrin and podocin may play pathogenetic roles in some patients with sporadic steroid resistant NS.
Because of its prognostic relevance, we advocate molecular genetic testing of LAMB2 in any case of prenatally detected nephrotic syndrome with negative results of NPHS1 mutational screening, especially in the presence of the typical sonomorphologic findings of the kidneys and the development of oligohydramnios.
Nephrotic syndrome (NS) in infancy includes NS of Finnish type (mutation of the nephrin gene), diffuse mesangial sclerosis (idiopathic or linked to WT1 mutation), idiopathic NS, most often steroid resistant, and NS related to infections during pregnancy (virus, syphilis, toxoplasmosis).