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Fourteen Monogenic Genes Account for 15% of Nephrolithiasis/Nephrocalcinosis

Lookup NU author(s): Dr Ann Marie Hynes, Dr Sarah RiceORCiD, Professor David Thwaites, Professor John SayerORCiD


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Nephrolithiasis is a prevalent condition with a high morbidity. Although dozens of monogenic causes have been identified, the fraction of single-gene disease has not been well studied. To determine the percentage of cases that can be molecularly explained by mutations in 1 of 30 known kidney stone genes, we conducted a high-throughput mutation analysis in a cohort of consecutively recruited patients from typical kidney stone clinics. The cohort comprised 272 genetically unresolved individuals (106 children and 166 adults) from 268 families with nephrolithiasis (n=256) or isolated nephrocalcinosis (n=16). We detected 50 likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 14.9% (40 of 268) of all cases; 20 of 50 detected mutations were novel (40%). The cystinuria gene SLC7A9 (n=19) was most frequently mutated. The percentage of monogenic cases was notably high in both the adult (11.4%) and pediatric cohorts (20.8%). Recessive causes were more frequent among children, whereas dominant disease occurred more abundantly in adults. Our study provides an in-depth analysis of monogenic causes of kidney stone disease. We suggest that knowledge of the molecular cause of nephrolithiasis and nephrocalcinosis may have practical implications and might facilitate personalized treatment.

Publication metadata

Author(s): Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, Wassner AJ, Nelson CP, Tasic V, Sayer JA, Hildebrandt F

Publication type: Article

Publication status: Published

Journal: Journal of the American Society of Nephrology

Year: 2015

Volume: 26

Issue: 3

Pages: 543-551

Print publication date: 01/03/2015

Online publication date: 08/10/2014

Acceptance date: 18/06/2014

ISSN (print): 1046-6673

ISSN (electronic): 1533-3450

Publisher: American Society of Nephrology


DOI: 10.1681/ASN.2014040388


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Funder referenceFunder name
Northern Counties Kidney Research Fund
6FY11-241March of Dimes Foundation
R01-DK088767National Institutes of Health