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Mutations in SLC26A1 Cause Nephrolithiasis.
- Source :
-
American journal of human genetics [Am J Hum Genet] 2016 Jun 02; Vol. 98 (6), pp. 1228-1234. Date of Electronic Publication: 2016 May 19. - Publication Year :
- 2016
-
Abstract
- 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.<br /> (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Anion Transport Proteins chemistry
Bicarbonates metabolism
Fluorescent Antibody Technique
Glycosylation
High-Throughput Nucleotide Sequencing
Humans
Immunoblotting
Nephrolithiasis pathology
Protein Conformation
Protein Folding
Protein Transport
Real-Time Polymerase Chain Reaction
Sequence Homology, Amino Acid
Sulfate Transporters
Sulfates metabolism
Anion Transport Proteins genetics
Anion Transport Proteins metabolism
Mutation genetics
Nephrolithiasis etiology
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6605
- Volume :
- 98
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of human genetics
- Publication Type :
- Academic Journal
- Accession number :
- 27210743
- Full Text :
- https://doi.org/10.1016/j.ajhg.2016.03.026