Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy

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Item Type:	Article
Title:	Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy
Creators Name:	Tinschert, S., Ruf, N., Bernascone, I., Sacherer, K., Lamorte, G., Neumayer, H.H., Nuernberg, P., Luft, F.C. and Rampoldi, L.
Abstract:	Background. Familial juvenile hyperuricaemic nephropathy (FJHN) is an autosomal-dominant disorder featuring hyperuricaemia, low fractional urate excretion, interstitial nephritis and chronic renal failure. The responsible gene UMOD was recently identified. UMOD encodes for uromodulin or Tamm-Horsfall glycoprotein, the most abundant protein in normal urine. We encountered a family with FJHN and identified a novel UMOD mutation in exon 6. Methods. We sequenced the gene in all family members, identified the mutation, and verified its presence in the affected members. We next performed functional studies of the mutant protein by immunofluorescence and FACS analysis on transfected cells. Results. The mutation p.C347G (c.1039T > G) results in a conserved cysteine to glycine amino acid substitution in the uromodulin zona pellucida (ZP) domain. The cell studies showed that the novel uromodulin mutation causes a delay in protein export to the plasma membrane due to its retention in the endoplasmic reticulum. Conclusions. We describe the first reported mutation mapping in the ZP uromodulin domain. Our data provide further evidence showing why the excretion of uromodulin is reduced in this syndrome.
Keywords:	Familial Juvenile Hyperuricaemic Nephropathy, Genetics, Interstitial Nephritis, Tamm-Horsfall Glycoprotein, Uric Acid, Uromodulin
Source:	Nephrology Dialysis Transplantation
ISSN:	0931-0509
Publisher:	Oxford University Press
Volume:	19
Number:	12
Page Range:	3150-3154
Date:	1 January 2004
Official Publication:	https://doi.org/10.1093/ndt/gfh524
PubMed:	View item in PubMed

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