Genetic Screening in Children with Challenging Nephrotic Syndrome

Genetic screening paradigms for the nephrotic syndrome (NS) in the developed

world are well established; however, screening in developing countries has received only minor

attention.

We retrospectively analyzed a cohort of all children who underwent genetic testing for

challenging NS from our registry in the 10-year interval from 2000 to 2010 and based on 58

patients aged 0–12 years with at least one of the following clinical diagnosis: Nonsyndromic

steroid-resistant nephrotic syndrome (SRNS), familial NS, and congenital NS.

Of these, 23 patients (~40%) had a history of familial disease occurrence. All cases were screened for NPHS2

and WT1 mutations by direct sequencing of all exons of the genes. In addition, all patients who

were diagnosed during the first three months of life were screened for NPHS1 mutations too. A

genetic disease cause was identified in 12 patients (20.7%); of these, five novel mutations, all in

NPHS2 accounting for 42% of all mutations and 9% of the cohort. Nine patients were found to

have NPHS2 mutations. Only one case with SRNS had a mutation in WT1. Of the five congenital

NS, two cases were found to have NPHS1 mutations and one case with NPHS2 mutation.

Therefore, mutations in NPHS2 were the most commonly identified and explained in 15.5% of

the screened patients and WT1 mutation in 1.7% of cases, whereas NPHS1 mutations were found

in 40% of congenital NS cases.

A genetic disease cause was identified in 20.7% of the screened

patients. Among 12 identified mutations, abnormalities in NPHS2 (n = 9) were most commonly

identified.