Journal article
Variants of unknown significance are common in brushite stone formers undergoing genetic testing for nephrolithiasis
Urolithiasis, Vol.53(1), 183
09/29/2025
DOI: 10.1007/s00240-025-01859-1
PMCID: PMC12479612
PMID: 41021020
Appears in UI Libraries Support Open Access
Abstract
Up to 40% of all kidney stone disease may have an underlying genetic contribution. Brushite stone formers are known to have high rates of stone recurrence and urine chemistry abnormalities, suggesting a possible intrinsic kidney abnormality which may contribute to brushite stone formation. In this study, we sought to determine the burden of genetic variants amongst brushite stone formers. An IRB approved prospective study of brushite stone formers was conducted. Patients with any brushite on stone analysis were eligible for enrollment. Genetic testing was done on peripheral blood derived DNA and assessed using a clinically available nephrolithiasis gene panel. Primary analysis assessed rates of genetic variants amongst brushite stone formers. Secondary analysis assessed for distinct patterns in urine chemistries in different genotypes. 15 patients (8 males) with a median age of 32 years (range 22–69) underwent genetic testing. 12 patients (80%) were reported to have a genetic variant, with 6 (40%) having multiple variants. Two patients had a heterozygous pathogenic or likely pathogenic variant in a gene that causes autosomal recessive disease. 9 (60%) patients had a variant of unknown significance. 10 (67%) patients had genetic variants associated with hypophosphatemic rickets. Genetic variants of unknown significance are common in brushite stone formers. Further work is needed to assess the significance of these variants and their role in the lithogenic process.
Details
- Title: Subtitle
- Variants of unknown significance are common in brushite stone formers undergoing genetic testing for nephrolithiasis
- Creators
- Tomas Paneque - University of Iowa Health CareKyle Berst - University of IowaMeenakshi Sambharia - University of IowaMelissa Swee - University of IowaMycah Kimble - University of IowaM. Adela Mansilla - University of IowaMargaret Freese - University of IowaChristie P. Thomas - University of IowaChad R. Tracy - University of IowaRyan L. Steinberg - University of Iowa Health Care
- Resource Type
- Journal article
- Publication Details
- Urolithiasis, Vol.53(1), 183
- DOI
- 10.1007/s00240-025-01859-1
- PMID
- 41021020
- PMCID
- PMC12479612
- NLM abbreviation
- Urolithiasis
- ISSN
- 2194-7228
- eISSN
- 2194-7236
- Publisher
- Springer Nature
- Grant note
- UM1TR004403; UM1TR004403; UM1TR004403 / National Center for Advancing Translational Sciences of the National Institutes of Health
- Language
- English
- Date published
- 09/29/2025
- Academic Unit
- Radiology; Stead Family Department of Pediatrics; Obstetrics and Gynecology; Nephrology; Urology; Otolaryngology; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984966800602771
Metrics
22 Record Views