NPHS2 homozygous p.R229Q variant

Potential modifier instead of causal effect in focal segmental glomerulosclerosis

Andrea Kerti, Rózsa Csohány, L. Wágner, Eszter Jávorszky, Erika Maka, K. Tory

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: The pathogenicity of the NPHS2 homozygous p.R229Q variant in steroid-resistant nephrotic syndrome (SRNS) is doubtful. While it has been reported in unaffected controls, it is enriched in patients with SRNS, suggesting pathogenicity. Case-Diagnosis/Treatment: A family with three members homozygous for the NPHS2 p.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. The affected son also harbors a heterozygous de novo, truncating PAX2 mutation (c.76dupG, p.V26Gfs*28), which can explain his chronic renal failure but which is rarely associated with FSGS. Conclusions: This family provides further evidence that homozygous p.R229Q in itself may not cause FSGS. Nevertheless, the rare association of FSGS to a PAX2 mutation may reflect the modifier effect of p.R229Q in the homozygous state. Such a modifier effect can also explain its enrichment in SRNS patients. Patients with homozygous p.R229Q should be screened for the causative mutation in a second gene.

Original languageEnglish
Pages (from-to)2061-2064
Number of pages4
JournalPediatric Nephrology
Volume28
Issue number10
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Focal Segmental Glomerulosclerosis
Nephrotic Syndrome
Steroids
Proteinuria
Mutation
Chronic Kidney Failure
Virulence
Nuclear Family
Fathers
Siblings
Genes
Therapeutics

Keywords

  • Nephrotic syndrome
  • NPHS2
  • Pathogenicity
  • PAX2
  • Podocin

ASJC Scopus subject areas

  • Nephrology
  • Pediatrics, Perinatology, and Child Health

Cite this

NPHS2 homozygous p.R229Q variant : Potential modifier instead of causal effect in focal segmental glomerulosclerosis. / Kerti, Andrea; Csohány, Rózsa; Wágner, L.; Jávorszky, Eszter; Maka, Erika; Tory, K.

In: Pediatric Nephrology, Vol. 28, No. 10, 10.2013, p. 2061-2064.

Research output: Contribution to journalArticle

Kerti, Andrea ; Csohány, Rózsa ; Wágner, L. ; Jávorszky, Eszter ; Maka, Erika ; Tory, K. / NPHS2 homozygous p.R229Q variant : Potential modifier instead of causal effect in focal segmental glomerulosclerosis. In: Pediatric Nephrology. 2013 ; Vol. 28, No. 10. pp. 2061-2064.
@article{5c7f7594b6c2479680b32be7e666c4d4,
title = "NPHS2 homozygous p.R229Q variant: Potential modifier instead of causal effect in focal segmental glomerulosclerosis",
abstract = "Background: The pathogenicity of the NPHS2 homozygous p.R229Q variant in steroid-resistant nephrotic syndrome (SRNS) is doubtful. While it has been reported in unaffected controls, it is enriched in patients with SRNS, suggesting pathogenicity. Case-Diagnosis/Treatment: A family with three members homozygous for the NPHS2 p.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. The affected son also harbors a heterozygous de novo, truncating PAX2 mutation (c.76dupG, p.V26Gfs*28), which can explain his chronic renal failure but which is rarely associated with FSGS. Conclusions: This family provides further evidence that homozygous p.R229Q in itself may not cause FSGS. Nevertheless, the rare association of FSGS to a PAX2 mutation may reflect the modifier effect of p.R229Q in the homozygous state. Such a modifier effect can also explain its enrichment in SRNS patients. Patients with homozygous p.R229Q should be screened for the causative mutation in a second gene.",
keywords = "Nephrotic syndrome, NPHS2, Pathogenicity, PAX2, Podocin",
author = "Andrea Kerti and R{\'o}zsa Csoh{\'a}ny and L. W{\'a}gner and Eszter J{\'a}vorszky and Erika Maka and K. Tory",
year = "2013",
month = "10",
doi = "10.1007/s00467-013-2542-4",
language = "English",
volume = "28",
pages = "2061--2064",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",
number = "10",

}

TY - JOUR

T1 - NPHS2 homozygous p.R229Q variant

T2 - Potential modifier instead of causal effect in focal segmental glomerulosclerosis

AU - Kerti, Andrea

AU - Csohány, Rózsa

AU - Wágner, L.

AU - Jávorszky, Eszter

AU - Maka, Erika

AU - Tory, K.

PY - 2013/10

Y1 - 2013/10

N2 - Background: The pathogenicity of the NPHS2 homozygous p.R229Q variant in steroid-resistant nephrotic syndrome (SRNS) is doubtful. While it has been reported in unaffected controls, it is enriched in patients with SRNS, suggesting pathogenicity. Case-Diagnosis/Treatment: A family with three members homozygous for the NPHS2 p.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. The affected son also harbors a heterozygous de novo, truncating PAX2 mutation (c.76dupG, p.V26Gfs*28), which can explain his chronic renal failure but which is rarely associated with FSGS. Conclusions: This family provides further evidence that homozygous p.R229Q in itself may not cause FSGS. Nevertheless, the rare association of FSGS to a PAX2 mutation may reflect the modifier effect of p.R229Q in the homozygous state. Such a modifier effect can also explain its enrichment in SRNS patients. Patients with homozygous p.R229Q should be screened for the causative mutation in a second gene.

AB - Background: The pathogenicity of the NPHS2 homozygous p.R229Q variant in steroid-resistant nephrotic syndrome (SRNS) is doubtful. While it has been reported in unaffected controls, it is enriched in patients with SRNS, suggesting pathogenicity. Case-Diagnosis/Treatment: A family with three members homozygous for the NPHS2 p.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. The affected son also harbors a heterozygous de novo, truncating PAX2 mutation (c.76dupG, p.V26Gfs*28), which can explain his chronic renal failure but which is rarely associated with FSGS. Conclusions: This family provides further evidence that homozygous p.R229Q in itself may not cause FSGS. Nevertheless, the rare association of FSGS to a PAX2 mutation may reflect the modifier effect of p.R229Q in the homozygous state. Such a modifier effect can also explain its enrichment in SRNS patients. Patients with homozygous p.R229Q should be screened for the causative mutation in a second gene.

KW - Nephrotic syndrome

KW - NPHS2

KW - Pathogenicity

KW - PAX2

KW - Podocin

UR - http://www.scopus.com/inward/record.url?scp=84883276755&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883276755&partnerID=8YFLogxK

U2 - 10.1007/s00467-013-2542-4

DO - 10.1007/s00467-013-2542-4

M3 - Article

VL - 28

SP - 2061

EP - 2064

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

IS - 10

ER -