Lookup NU author(s): Professor John Sayer
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
Nephrolithiasis, a condition in which urinary supersaturation leads to stone formation in the urinary system, affects about 5%-10% of individuals worldwide at some point in their lifetime and results in significant medical costs and morbidity. To date, mutations in more than 30 genes have been described as being associated with nephrolithiasis, and these mutations explain about 15% of kidney stone cases, suggesting that additional nephrolithiasis-associated genes remain to be discovered. To identify additional genes whose mutations are linked to nephrolithiasis, we performed targeted next-generation sequencing of 18 hypothesized candidate genes in 348 unrelated individuals with kidney stones. We detected biallelic mutations in SLC26A1 (solute carrier family 26 member 1) in two unrelated individuals with calcium oxalate kidney stones. We show by immunofluorescence, immunoblotting, and glycosylation analysis that the variant protein mimicking p.Thr185Met has defects in protein folding or trafficking. In addition, by measuring anion exchange activity of SLC26A1, we demonstrate that all the identified mutations in SLC26A1 result in decreased transporter activity. Our data identify SLC26A1 mutations as causing a recessive Mendelian form of nephrolithiasis.
Author(s): Gee HY, Jun I, Braun DA, Lawson JA, Halbritter J, Shril S, Nelson CP, Tan WZ, Stein D, Wassner AJ, Ferguson MA, Gucev Z, Sayer JA, Milosevic D, Baum M, Tasic V, Lee MG, Hildebrandt F
Publication type: Article
Publication status: Published
Journal: American Journal of Human Genetics
Print publication date: 02/06/2016
Online publication date: 19/05/2016
Acceptance date: 25/03/2016
Date deposited: 13/07/2016
ISSN (print): 0002-9297
ISSN (electronic): 1537-6605
Publisher: Cell Press
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