Congenital nephrotic syndrome is an inherited autosomal recessive disorder characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, edema, and minimal glomerular changes. Majority of nephrotic syndrome (NS) occurs as a sporadic form, the incidence of familial cases is from 3 to 5%. Mutations of seven genes, NPHS1 (19q13.1), NPHS2 (1q25-31), ACTN4 (19q13), CD2AP, WT1, TRPC6 (11q21-22), and LAMB2, have been recognized to date as responsible for various forms of NS. Proteins encoded by these genes influence the function of the podocytes. Podocin is an integral membrane protein encoded by NPHS2, which is mapped to 1q25-31 and is exclusively expressed in glomerular podocytes. NPHS2 mutations are responsible for autosomal recessive familial steroidresistant nephrotic syndrome (SRNS) with minor glomerular abnormalities or focal segmental glomerulosclerosis (FSGS), which is characterized by early childhood onset and rapid progression to chronic renal insufficiency. It has been demonstrated that sporadic SRNS and heavy proteinuria are also due to NPHS2 gene mutations. In this study, we ascertained a consanguineous Pakistani family with congenital nephritic syndrome. By genetic linkage analysis we mapped the disease phenotype NPHS2 gene locus. All eight exons and exon-intron boundaries of NPHS2 gene were analyzed by using the polymerase chain reaction and direct sequencing. A pathogenic 9bp deletion (704del9) mutation in exon 5 of NPHS2 gene, resulting in a 3-amino acid deletion (residues 236-238) was associated with the disease in Pakistani family.

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