El. Romppanen et I. Mononen, Detection of the Finnish-type congenital nephrotic syndrome by restrictionfragment length polymorphism and dual-color oligonucleotide ligation assays, CLIN CHEM, 46(6), 2000, pp. 811-816
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.