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Cystinuria: an inborn cause of urolithiasis

Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two g...

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Autores principales: Eggermann, Thomas, Venghaus, Andreas, Zerres, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464901/
https://www.ncbi.nlm.nih.gov/pubmed/22480232
http://dx.doi.org/10.1186/1750-1172-7-19
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author Eggermann, Thomas
Venghaus, Andreas
Zerres, Klaus
author_facet Eggermann, Thomas
Venghaus, Andreas
Zerres, Klaus
author_sort Eggermann, Thomas
collection PubMed
description Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy subunit rBAT of a renal b(0,+) transporter while SLC7A9 (chromosome 19q12) encodes its interacting light subunit b(0,+)AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.
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spelling pubmed-34649012012-10-06 Cystinuria: an inborn cause of urolithiasis Eggermann, Thomas Venghaus, Andreas Zerres, Klaus Orphanet J Rare Dis Review Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy subunit rBAT of a renal b(0,+) transporter while SLC7A9 (chromosome 19q12) encodes its interacting light subunit b(0,+)AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies. BioMed Central 2012-04-05 /pmc/articles/PMC3464901/ /pubmed/22480232 http://dx.doi.org/10.1186/1750-1172-7-19 Text en Copyright ©2012 Eggermann et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Eggermann, Thomas
Venghaus, Andreas
Zerres, Klaus
Cystinuria: an inborn cause of urolithiasis
title Cystinuria: an inborn cause of urolithiasis
title_full Cystinuria: an inborn cause of urolithiasis
title_fullStr Cystinuria: an inborn cause of urolithiasis
title_full_unstemmed Cystinuria: an inborn cause of urolithiasis
title_short Cystinuria: an inborn cause of urolithiasis
title_sort cystinuria: an inborn cause of urolithiasis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464901/
https://www.ncbi.nlm.nih.gov/pubmed/22480232
http://dx.doi.org/10.1186/1750-1172-7-19
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