Zagorec, N., Calamel, A., Delaporte, M. et al. (24 more authors) (2024) Clinical spectrum and prognosis of atypical autosomal dominant polycystic kidney disease caused by monoallelic pathogenic variants of IFT140. American Journal of Kidney Diseases. ISSN 0272-6386
Abstract
Rationale & Objective
Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.
Study Design
Case series.
Setting & Participants
Seventy-five among 2797 European individuals with ADPKD-like phenotypes who underwent genetic testing that revealed pLoF IFT140-variants.
Findings
The 75 individuals (median age 56 years, 53.3% females) were from 61 families and were found to have 41 different monoallelic pLoF IFT140-variants. The majority of individuals presented with large, exophytic kidney cysts (median [range] total kidney volume 688 ml [201-4139]), and 90.2% were classified using the Mayo Imaging Classification as Mayo Class 2A. Arterial hypertension was present in 50.7% of the individuals (median [range] age at diagnosis 59 years [29-73]). Only one patient developed kidney failure (at age 69 years). A significant difference in age-adjusted eGFR between male and female patients was observed (P<0.001). 56.3% of the individuals over the age of 60 years had an eGFR less than 60ml/min/1.73m2. The estimated genetic prevalence of monoallelic pLoF IFT140 variants was 19.76 (95%CI=18.8-20.7) and 27.89 (95%CI=23.8-31.9) per 10,000 in the Genome Aggregation Database and the 100,000 Genomes Project (100kG), respectively. CyKD (ICD-10 Q61) was associated with pLoF IFT140 variants (P=2.9x10-9, OR=5.6 (3.3-9.2)) only in 100kG.
Study Limitations
Retrospective study; younger patients and patients with milder forms of IFT140-related CyKD may not be diagnosed.
Conclusions
Individuals with monoallelic IFT140 pLoF variants are likely to develop kidney cysts atypical of classical ADPKD and generally have a favorable kidney prognosis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. Except as otherwise noted, this author-accepted version of a journal article published in American Journal of Kidney Diseases is made available via the University of Sheffield Research Publications and Copyright Policy under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ |
Keywords: | ADPKD-like spectrum; IFT140; autosomal dominant polycystic kidney disease (ADPKD); case series; inherited kidney diseases; kidney function; loss of function variants; monoallelic IFT140-variants; polycystic kidney disease |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Jan 2025 11:24 |
Last Modified: | 29 Jan 2025 11:24 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1053/j.ajkd.2024.10.009 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222549 |