We present a 12-year-old girl with rapidly progressive FSGS and end-stage renal disease in her native kidneys associated with heterozygous mutations in NPHS1 and in NPHS2, suffering from early post-transplant recurrence.
Mutations in podocin are known to be associated with steroid-resistant NS and rapid progression to end-stage renal disease, thus signifying its role in maintaining SD integrity and podocyte function.
The minor allele in NPHS2 markedly changed the APOL1-ESKD association odds ratio (OR) from 7.03 to 1.76 (∼50% reduction in effect per copy of the minor allele), rs2802723 changed the OR from 5.1 to 10.5, and rs8014363 increased the OR from 4.8 to 9.5.
A family with three members homozygous for the NPHS2p.R229Q variant is presented: a 37-year-old patient who was diagnosed with proteinuria at age 7 months, focal segmental glomerulosclerosis (FSGS) at age 20 years, and end-stage renal disease (ESRD) at age 33 years, his 59 year-old father and his 40 year-old brother, both unaffected with no proteinuria.
To investigate the potential role of this gene in ESRD, we sequenced all coding regions and approximately 2 kb of upstream promoter sequence of NPHS2 in 96 unrelated AA nondiabetic ESRD cases and 96 healthy population-based AA controls, and assessed several single nucleotide polymorphisms (SNPs) for association in a larger case-control sample.
To investigate the potential role of this gene in ESRD, we sequenced all coding regions and approximately 2 kb of upstream promoter sequence of NPHS2 in 96 unrelated AA nondiabetic ESRD cases and 96 healthy population-based AA controls, and assessed several single nucleotide polymorphisms (SNPs) for association in a larger case-control sample.
We analyzed these reported mutations in ACTN4 and podocin in five patients with chronic renal failure due to therapy-resistant FSGS by direct sequencing of polymerase chain reaction products of ACTN4 and podocin.
Mutations of NPHS1 or NPHS2, the genes encoding for nephrin and podocin, lead to early onset of heavy proteinuria, and rapid progression to end-stage renal disease, suggesting that both proteins are essential for the integrity of the glomerular filter.
Mutations of NPHS1 or NPHS2, the genes encoding for nephrin and podocin, lead to early onset of heavy proteinuria, and rapid progression to end-stage renal disease, suggesting that both proteins are essential for the integrity of the glomerular filter.