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

Background: Congenital nephrotic syndrome of Finnish type (NPHS1) is an aut osomal recessive disorder characterized by severe proteinuria of intrauteri ne onset. Ninety-four percent of the Finnish NPHSI chromosomes have been re ported to carry either a 2-bp deletion in exon 2 (Fin(Major)) or a nonsense mutation in exon 26 (Fin(Minor)) of the NPHSI 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 de tection of the NPHSI mutations: a PCR-restriction fragment length polymorph ism (PCR-RFLP) and a dual-color oligonucleotide ligation assay (OLA). The d ual-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, indicati ng 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 diagnosi s and carrier screening of the major mutations that cause NPHS1. (C) 2000 A merican Association for Clinical Chemistry.