Authors: Stephen Tonna Yan Yan Wang Diane Wilson Lin Rigby Tania Tabone Richard Cotton Judy Savige
Publish Date: 2008/08/26
Volume: 23, Issue: 12, Pages: 2201-2207
Abstract
Thinbasementmembrane nephropathy TBMN is characterized by persistent dysmorphic hematuria and the presence of proteinuria is a risk factor for renal impairment TBMN is often due to mutations in the COL4A3 and COL4A4 genes and this study determined whether additional mutations in genes encoding other structures in the glomerular filtration barrier contributed to the development of proteinuria Fiftysix unrelated individuals with TBMN including 18 32 with proteinuria ≥ 300 mg/L and ten 18 with proteinuria ≥ 500 mg/L were studied Deoxyribonucleic acid DNA was screened for NPHS2 mutations and variants R138Q and P375L using singlestranded conformational analysis SSCA and for the R229Q mutation by sequencing DNA was also screened for ACTN4 mutations R229Q was more common in patients with TBMN and proteinuria ≥ 500 mg/L p 005 and a possible NPHS2 mutation 671GA R224H was identified in one patient with proteinuria 700 mg/L No other NPHS2 variants correlated with proteinuria and no ACTN4 mutations were found Individuals with TBMN and R229Q are carriers of the autosomal recessive forms of both Alport syndrome and familial focal segmental glomerulosclerosis FSGS The early demonstration of R229Q in individuals with TBMN may indicate those at increased risk of proteinuria and renal impairmentThis work was supported in part by the National Health and Medical Research Council of Australia and Kidney Health Australia This work was presented as a poster at the Annual Meeting of the American Society of Nephrology 2003 and at the 6th International Podocyte Conference 2006
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