Background: Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal recessive disorder mainly caused by mutations in the nephrin gene (NPHS1). The frequency of this gene is highest in Finland but the condition occurs in all populations, with and without Finnish ancestry. The NPHS1 gene is located in the chromosomal region 19q13.1 and consists of 29 exons.
Methods: Polymerase chain reaction (PCR), restriction and sequence analyses were used to screen 15 CNF Italian patients for mutations in this gene.
Results: No Italian patients had the typical Finnish mutations, a 2bp deletion in exon 2 (Fin-major) and a nonsense mutation in exon 26 (Fin-minor). We found 13 mutations including deletions, insertions, nonsense and missense mutations. Seven of these have never been described before. We also found one nucleotide change in the promoter region and one common polymorphism. NPHS1 missense mutations were confirmed by analysis of a healthy control population.
Conclusions: Our study provides further evidence that loss of function of the nephrin gene is the main cause of congenital nephrotic syndrome of the Finnish type in Italian patients.