Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.

Details

Serval ID
serval:BIB_E4DCD4E23355
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1.
Journal
Kidney international
Author(s)
Olinger E., Hofmann P., Kidd K., Dufour I., Belge H., Schaeffer C., Kipp A., Bonny O., Deltas C., Demoulin N., Fehr T., Fuster D.G., Gale D.P., Goffin E., Hodaňová K., Huynh-Do U., Kistler A., Morelle J., Papagregoriou G., Pirson Y., Sandford R., Sayer J.A., Torra R., Venzin C., Venzin R., Vogt B., Živná M., Greka A., Dahan K., Rampoldi L., Kmoch S., Bleyer A.J., Devuyst O.
ISSN
1523-1755 (Electronic)
ISSN-L
0085-2538
Publication state
Published
Issued date
09/2020
Peer-reviewed
Oui
Volume
98
Number
3
Pages
717-731
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMOD and MUC1. The lack of clinical recognition and the small size of cohorts have slowed the understanding of disease ontology and development of diagnostic algorithms. We analyzed two registries from Europe and the United States to define genetic and clinical characteristics of ADTKD-UMOD and ADTKD-MUC1 and develop a practical score to guide genetic testing. Our study encompassed 726 patients from 585 families with a presumptive diagnosis of ADTKD along with clinical, biochemical, genetic and radiologic data. Collectively, 106 different UMOD mutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1 mutations in 72/205 (35.1%) of the families that are UMOD-negative (83 patients). The median kidney survival was significantly shorter in patients with ADTKD-MUC1 compared to ADTKD-UMOD (46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMOD compared to ADTKD-MUC1 (30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1 had normal urinary excretion of uromodulin and distribution of uromodulin in tubular cells. A diagnostic algorithm based on a simple score coupled with urinary uromodulin measurements separated patients with ADTKD-UMOD from those with ADTKD-MUC1 with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMOD mutation. Thus, ADTKD-UMOD is more frequently diagnosed than ADTKD-MUC1, ADTKD subtypes present with distinct clinical features, and a simple score coupled with urine uromodulin measurements may help prioritizing genetic testing.
Keywords
Europe, Genetic Testing, Humans, Mucin-1/genetics, Mutation, Polycystic Kidney, Autosomal Dominant/diagnosis, Polycystic Kidney, Autosomal Dominant/genetics, Uromodulin/genetics, diagnostic score, dominant kidney disease, gout, mucin-1, uromodulin
Pubmed
Web of science
Open Access
Yes
Create date
10/06/2020 21:44
Last modification date
30/06/2021 5:34
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