NPHS2 homozygous p.R229Q variant: potential modifier instead of causal effect in focal segmental glomerulosclerosis.
Pediatr Nephrol
; 28(10): 2061-4, 2013 Oct.
Article
em En
| MEDLINE
| ID: mdl-23800802
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Glomerulosclerose Segmentar e Focal
/
Peptídeos e Proteínas de Sinalização Intracelular
/
Genes Modificadores
/
Homozigoto
/
Proteínas de Membrana
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article