Detection of the Finnish-type congenital nephrotic syndrome by restriction fragment length polymorphism and dual-color oligonucleotide ligation assays.

BACKGROUND Congenital nephrotic syndrome of Finnish type (NPHS1) is an autosomal recessive disorder characterized by severe proteinuria of intrauterine onset. Ninety-four percent of the Finnish NPHS1 chromosomes have been reported to carry either a 2-bp deletion in exon 2 (Fin(Major)) or a nonsense mutation in exon 26 (Fin(Minor)) of the NPHS1 gene. The high prevalence of only two mutations in the Finnish population enables the use of molecular techniques in the diagnosis of NPHS1 and for carrier screening. METHODS AND RESULTS We describe two different molecular methods for the detection of the NPHS1 mutations: a PCR-restriction fragment length polymorphism (PCR-RFLP) and a dual-color oligonucleotide ligation assay (OLA). The dual-color OLA, which enables simultaneous detection of the NPHS1 Fin(Major) and Fin(Minor) mutations, can be used for rapid analysis of large sets of samples. The analysis of 2004 Finnish blood samples revealed 34 carriers of the Fin(Major) mutation and 1 carrier of the Fin(Minor) mutation, indicating a carrier frequency of 1:59 (95% confidence interval, 1:89-1:44) for the NPHS1 Fin(Major) mutation and 1:2004 (95% confidence interval, 0 to 1:677) for the NPHS1 Fin(Minor) mutation, respectively. CONCLUSION PCR-RFLP and dual-color OLA are suitable for molecular diagnosis and carrier screening of the major mutations that cause NPHS1.