Structure of the gene for congenital nephrotic syndrome of the Finnish type (NPHS1) and characterization of mutations

Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal r ecessive disorder that is caused by mutations in the recently discovered ne phrin gene, NPHS1 (AF035835). The disease, which belongs to the Finnish dis ease heritage, exists predominantly in Finland, but many cases have been ob served else:where in Europe and North America. The nephrin gene consists of 29 exons spanning 26 kb in the chromosomal region 19q13.1. In the present study, the genomic structure of the nephrin gene was analyzed, and 35 NPHS1 patients were screened for the presence of mutations in the gene. A total of 32 novel mutations, including deletions; insertions; nonsense, missense, and splicing mutations; and two common polymorphisms were found. Only two Swedish and four Finnish patients had the typical Finnish mutations: a 2-bp deletion in exon 2 (Fin(major)) or a nonsense mutation in exon 26 (Fin(min or)). In seven cases, no mutations were found in the coding region of the N PHS1 gene or in the immediate 5'-flanking region. These patients may have m utations elsewhere in the promoter, in intron areas, or in a gene encoding another protein that interacts with nephrin.