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

作者：Edwards Noel; Olinger Eric; Adam Jennifer; Kelly Michael; Schiano Guglielmo; Ram**ottom Simon A; Sandford Richard; Devuyst Olivier^*; Sayer John A^*

来源：Nephrology Dialysis Transplantation, 2017, 32(12): 1994-1999.

DOI：10.1093/ndt/gfx066

• gout
• homozygous mutation
• Tamm-Horsfall protein
• tubulointerstitial kidney disease
• uromodulin

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.

• 出版日期2017-12
• 单位河北医科大学