Two novel NPHS1 mutations in a Chinese family with congenital nephrotic syndrome.

Congenital nephrotic syndrome of the Finnish type (CNF) is a lethal, autosomal recessive disorder mainly caused by mutations in the NPHS1 gene; it is found at a relatively high frequency in Finns. We investigated the disease-causing mutations in a Chinese family with CNF and developed a prenatal genetic diagnosis for their latest pregnancy. Mutation analysis was made of all exons and exon/intron boundaries of NPHS1 in the fetus, parents and 50 unrelated controls using PCR and direct sequencing. A heterozygous nonsense mutation within exon 20 (c.2783C>A) and a missense mutation within exon 17 (c.2225T>C) in NPHS1 were detected in the proband's father and mother, respectively, but were not found in the fetus or in 50 unrelated controls. Two novel mutations of c.2783C>A and c.2225T>C in NPHS1 were found to be causative in this Chinese CNF family with no known Finnish ancestry. The most recent sibling did not inherit these two mutations and hence was unaffected with CNF. Determining the cumulative number and ethnic distribution of known mutations can help expedite further study of the pathogenesis of CNF.