Recent evidence suggests that NPHS2-R229Q, a podocin polymorphism, may contribute to proteinuria in TBMN and to micro-albuminuria in the general population.
R229Q was more common in patients with TBMN and proteinuria > or = 500 mg/L (p < 0.05), and a possible NPHS2 mutation (671G>A, R224H) was identified in one patient with proteinuria 700 mg/L.
In one adult patient, there were two polymorphisms, p.P20L and p.R229Q, in trans-heterozygous state, which could contribute to steroid-resistant nephrotic syndrome.
In steroid-resistant nephrotic syndrome (SRNS) Machuca et al. report that mutations of the recessive podocin gene cause adult-onset SRNS if the R229Q genetic variant occurs in a compound heterozygous state with another podocin mutation.
Our study shows that compound heterozygosity for p.R229Q is associated with adult-onset steroid-resistant NS, mostly among patients of European and South American origin.
Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02).
The compound heterozygous mutation in NPHS2 may explain the development of SRNS in this family. p.Arg71X is a novel disease-causing mutation leading to a deficient expression of podocin.
We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.
We identified a novel mutation of NPHS2(467_468insT and 503G>A) in a Chinese family with autosomal recessive SRNS using polymerase chain re-action, denaturing high-performance liquid chromatography, and DNA sequencing techniques.
In one adult patient, there were two polymorphisms, p.P20L and p.R229Q, in trans-heterozygous state, which could contribute to steroid-resistant nephrotic syndrome.
Our study shows that compound heterozygosity for p.R229Q is associated with adult-onset steroid-resistant NS, mostly among patients of European and South American origin.
In steroid-resistant nephrotic syndrome (SRNS) Machuca et al. report that mutations of the recessive podocin gene cause adult-onset SRNS if the R229Q genetic variant occurs in a compound heterozygous state with another podocin mutation.
Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02).
In one adult patient, there were two polymorphisms, p.P20L and p.R229Q, in trans-heterozygous state, which could contribute to steroid-resistant nephrotic syndrome.