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Schönauer, R.* ; Scherer, L.* ; Nemitz-Kliemchen, M.* ; Hagemann, T. ; Hantmann, E.* ; Seidel, A.* ; Müller, L.* ; Kehr, S.* ; Voigt, C.* ; Stolzenburg, J.U.* ; Halbritter, J.*

Systematic assessment of monogenic etiology in adult-onset kidney stone formers undergoing urological intervention–evidence for genetic pretest probability.

Am. J. Med. Genet. C 190, 279-288 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Kidney stone disease (KSD) is a prevalent condition associated with high morbidity, frequent recurrence, and progression to chronic kidney disease (CKD). The etiology is multifactorial, depending on environmental and genetic factors. Although monogenic KSD is frequent in children, unbiased prevalence data of heritable forms in adults is scarce. Within 2 years of recruitment, all patients hospitalized for urological kidney stone intervention at our center were consecutively enrolled for targeted next generation sequencing (tNGS). Additionally, clinical and metabolic assessments were performed for genotype–phenotype analyses. The cohort comprised 155 (66%) males and 81 (34%) females, with a mean age at first stone of 47 years (4–86). The diagnostic yield of tNGS was 6.8% (16/236), with cystinuria (SLC3A1, SLC7A9), distal renal tubular acidosis (SLC4A1), and renal phosphate wasting (SLC34A1, SLC9A3R1) as underlying hereditary disorders. While metabolic syndrome traits were associated with late-onset KSD, hereditary KSD was associated with increased disease severity in terms of early-onset, frequent recurrence, mildly impaired kidney function, and common bilateral affection. By employing systematic genetic analysis to a less biased cohort of common adult kidney stone formers, we demonstrate its diagnostic value for establishing the underlying disorder in a distinct proportion. Factors determining pretest probability include age at first stone (<40 years), frequent recurrence, mild CKD, and bilateral KSD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cystinuria ; Genetics ; Kidney Stone Disease ; Nephrocalcinosis ; Nephrolithiasis ; Urolithiasis
ISSN (print) / ISBN 1552-4868
e-ISSN 1552-4876
Journal American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Quellenangaben Volume: 190, Issue: 3, Pages: 279-288 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Fritz Thyssen Stiftung

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