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A novel homozygous UMOD mutation reveals gene dosage effects on uromodulin processing and urinary excretion

Lookup NU author(s): Dr Noel Edwards, Dr Simon RamsbottomORCiD, Professor John SayerORCiD

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Abstract

Heterozygous mutations in UMOD encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). We describe the exceptional case of a patient from a consanguineous family carrying a novel homozygous UMOD mutation (p.C120Y) affecting a conserved cysteine residue within the EGF-like domain III of uromodulin. Comparison of heterozygote and homozygote mutation carriers revealed a gene dosage effect with unprecedented low levels of uromodulin and aberrant uromodulin fragments in the urine of the homozygote proband. Despite an amplified biological effect of the homozygote mutation, the proband did not show a strikingly more severe clinical evolution nor was the near absence of urinary uromodulin associated with urinary tract infections or kidney stones

Publication metadata

Author(s): Edwards N, Olinger E, Adam J, Kelly M, Schiano G, Ramsbottom SA, Sandford R, Devuyst O, Sayer JA

Publication type: Article

Publication status: Published

Journal: Nephrology Dialysis Transplantation

Year: 2017

Online publication date: 10/06/2017

Acceptance date: 19/03/2017

Date deposited: 30/06/2017

ISSN (print): 0931-0509

ISSN (electronic): 1460-2385

Publisher: Oxford University Press

URL: https://doi.org/10.1093/ndt/gfx066

DOI: 10.1093/ndt/gfx066

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