Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome

Abstract

Congenital nephrotic syndrome, Finnish type (CNF or NPHS1), is an autosomal recessive disease characterized by massive proteinuria and development of nephrotic syndrome shortly after birth. The disease is most common in Finland, but many patients have been identified in other populations. The disease is caused by mutations in the gene for nephrin which is a key component of the glomerual ultrafilter, the podocyte slit diaphragm. A total of 30 mutations have been reported in the nephrin gene in patients with congenital nephrotic syndrome worldwide. In the Finnish population, two main mutations have been found. These two nonsense mutations account for over 94% of all mutations in Finland. Most mutations found in non-Finnish patients are missense mutations, but they include also nonsense and splice site mutations, as well as deletions and insertions. This mutation update summarizes the nature of all previously reported nephrin mutations and, additionally, describes 20 novel mutations recently identified in our laboratory.

β-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity

“…The fact that the most C-terminal known nephrin mutation R1160X is sufficient to cause the full clinical phenotype of the Nephrotic syndrome of the Finnish type (22,23) strengthens the importance of those C-terminal amino acids that enclose the podocin-and ␤-arrestin2-regulatory site. In addition, as in other interacting partners of ␤-arrestins such as the orexin-1 receptor (24), domains adjacent to the ␤-arrestin binding site have been shown to have regulatory influences.…”

Novel NPHS1 splice site mutations in a Chinese child with congenital nephrotic syndrome

“…To date, more than 160 different mutations, including deletions, insertions, nonsense, missense, splice site, and promoter mutations, have been reported both in Finnish and non-Finnish patients (Lenkkeri et al, 1999;Beltcheva et al, 2001;Yu et al, 2012;Ameli et al, 2013).…”

Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

“…There is growing evidence that mutations in genes coding for slit diaphragm proteins frequently also occur in sporadic NS and are associated with potentially variable clinical outcome (3)(4)(5)(6)(7)(8)(9). Most reports have focused on monogenic diseases involving two major genesnephrin (NPHS1) and podocin (NPHS2)-that together cause almost 60% of the cases of NS in those who are younger than 1 yr and in adolescents (10).…”