Uromodulin kidney disease (UKD) is a subtype of autosomal dominant tubulointerstitial kidney disease (ADTKD), and is a rare cause of renal failure and gout in young people.
<b>Introduction:</b> Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the <i>MUC1, UMOD, HNF1B, REN</i>, and <i>SEC61A1</i> genes.
Mutations in nephrin (NPHS1), podocin (NPHS2), laminin β2 (LAMB2), and α-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV α chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease.
This study demonstrates that precise positioning of the causative mutation(s) and identification of other coding and noncoding sequence variants in ADTKD-MUC1 is feasible.
Immunostaining with our MUC1-fs antibodies and an MUC1 antibody showed that both proteins are readily detectable in human ADTKD-<i>MUC1</i> kidneys, with mucin 1 localized to the apical membrane and MUC1-fs abundantly distributed throughout the cytoplasm.
We aimed to establish the prevalence of genetic kidney diseases, ADTKD and ADTKD-UMOD in adult chronic kidney disease (CKD) patients, and to investigate characteristic features.
Autosomal dominant tubulointerstitial kidney disease associated to the MUC1 gene (ADTKD-MUC1; formerly MCKD1) belongs to a heterogeneous group of rare hereditary kidney diseases that is prototypically caused by frameshift mutations in the MUC1 repeat domain.
There are 3 major forms of autosomal dominant tubulointerstitial kidney disease (ADTKD): ADTKD due to UMOD mutations, MUC1 mutations, and mutations in the REN gene encoding renin.
ADTKD-<i>UMOD</i>, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER) of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R).
Heterozygous mutations in UMOD encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD).
UMOD-associated kidney disease has been proposed as a logical diagnostic label to replace FJHN, but given all these other mutations, an over-arching diagnostic term of 'autosomal dominant tubulointerstitial kidney disease' (ADTKD) has been recently adopted.
Testing for the cytosine insertion in the VNTR of the MUC1 gene in a cohort of Italian patients with autosomal dominant tubulointerstitial kidney disease.
Mucin-1 kidney disease, previously described as medullary cystic kidney disease type 1 (MCKD1, OMIM 174000), is an autosomal dominant tubulointerstitial kidney disease recently shown to be caused by a single-base insertion within the variable number tandem repeat region of the MUC1 gene.