{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:59209"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:59209","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Mutationsspektrum in den Genen SLC3A1 und SLC7A9 bei jugendlichen Cystinuriepatienten","abstract":"Cystinuria is a hereditary kidney stone disease which is caused by a renal tubular defect of reabsorption of cystine and the dibasic amino acids lysine, arginine and ornithine. Once the threshold of solubility is exceeded cystine precipitates and subsequently patients suffer from recurrent kidney stone formation. Stone formation and resulting complications characterize the cause of the disease. The incidence in the common population is about 1:7000. Cystinuria contributes to approximately 1% of adult nephrolithiasis and 6-8% of childhood nephrolithiasis. The disease can be subdivided biochemically on the basis of amino acid concentrations in urine of patients and their relatives into different subtypes, which are associated with specific mutations in the SLC3A1 and SLC7A9 genes. Type I cystinuria is caused by mutations in the SLC3A1 gene and follows an autosomal recessive mode of inheritance whereas non Type I cystinuria is caused by mutations in the SLC7A9 gene and exhibits an autosomal dominant mode of inheritance with variable penetrance due to elevated concentrations of amino acids in urine in heterozygotes. Double heterozygous mutations in both genes as well as an isolated form of cystinuria have also been described. The aim of this study was to determine the contribution of the known cystinuria genes SLC3A1 and SLC7A9 to early manifesting disease forms. Therefore a study population of 21 pediatric patients of 16 families and 10 unclassified patients with a history of recurrent nephrolithiasis were investigated. Mutation detection rates for the alleles typed as type I or non type one of the non related pediatric patients were 54% (6/11) for the SLC3A1 gene and 25% (2/8) for the SLC7A9 gene. The remaining 11 unclassified alleles showed 2 mutations in the SLC3A1 and 2 mutations in the SLC7A9 gene. The detection rates for the 10 unclassified patients were 55% (11/20) for the SLC3A1- and 10% (2/20) for the SLC7A9 gene. This corresponds to a mutation detection rate of 50% for the whole study population. Within this study the hitherto unknown deletion c1749_c1751del in exon 10 of the SLC3A1 gene, two point mutations (A224V and A331V), a deletion c949_c951del in exon 8 as well as the polymorphism c1328C/T in exon 11 of the SLC7A9 gene could be identified. The results of this study confirmed the crucial role of the hitherto known genes SLC3A1 and SLC7A9 in the pathogenesis of the disease. The identification of new sequence variants in both genes shows that further investigation of the coding sequences as well as the promotor and intron sequences will extend the spectrum of so far described mutations. Comparison of population specific frequencies of known polymorphisms may reveal linkage of specific haplotypes to further factors which are related to the disease. Mutation detection rates of the study population as a whole especially with regard to the pediatric patients with early manifesting disease indicate that further genes contribute to the aetiology and the course of the disease.","abstract_html":"Cystinuria is a hereditary kidney stone disease which is caused by a renal tubular defect of reabsorption of cystine and the dibasic amino acids lysine, arginine and ornithine. Once the threshold of solubility is exceeded cystine precipitates and subsequently patients suffer from recurrent kidney stone formation. Stone formation and resulting complications characterize the cause of the disease. The incidence in the common population is about 1:7000. Cystinuria contributes to approximately 1% of adult nephrolithiasis and 6-8% of childhood nephrolithiasis. The disease can be subdivided biochemically on the basis of amino acid concentrations in urine of patients and their relatives into different subtypes, which are associated with specific mutations in the SLC3A1 and SLC7A9 genes. Type I cystinuria is caused by mutations in the SLC3A1 gene and follows an autosomal recessive mode of inheritance whereas non Type I cystinuria is caused by mutations in the SLC7A9 gene and exhibits an autosomal dominant mode of inheritance with variable penetrance due to elevated concentrations of amino acids in urine in heterozygotes. Double heterozygous mutations in both genes as well as an isolated form of cystinuria have also been described. The aim of this study was to determine the contribution of the known cystinuria genes SLC3A1 and SLC7A9 to early manifesting disease forms. Therefore a study population of 21 pediatric patients of 16 families and 10 unclassified patients with a history of recurrent nephrolithiasis were investigated. Mutation detection rates for the alleles typed as type I or non type one of the non related pediatric patients were 54% (6/11) for the SLC3A1 gene and 25% (2/8) for the SLC7A9 gene. The remaining 11 unclassified alleles showed 2 mutations in the SLC3A1 and 2 mutations in the SLC7A9 gene. The detection rates for the 10 unclassified patients were 55% (11/20) for the SLC3A1- and 10% (2/20) for the SLC7A9 gene. This corresponds to a mutation detection rate of 50% for the whole study population. Within this study the hitherto unknown deletion c1749_c1751del in exon 10 of the SLC3A1 gene, two point mutations (A224V and A331V), a deletion c949_c951del in exon 8 as well as the polymorphism c1328C/T in exon 11 of the SLC7A9 gene could be identified. The results of this study confirmed the crucial role of the hitherto known genes SLC3A1 and SLC7A9 in the pathogenesis of the disease. The identification of new sequence variants in both genes shows that further investigation of the coding sequences as well as the promotor and intron sequences will extend the spectrum of so far described mutations. Comparison of population specific frequencies of known polymorphisms may reveal linkage of specific haplotypes to further factors which are related to the disease. Mutation detection rates of the study population as a whole especially with regard to the pediatric patients with early manifesting disease indicate that further genes contribute to the aetiology and the course of the disease.","abstract_has_math":false,"creators":["Botzenhart, Elke Maria"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Zerres, Klaus"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2003,"date_issued":"2003","date_published":"2003","updated_at":"2026-07-30T19:42:39Z","subjects":["info:eu-repo/classification/ddc/610","Medizin","Cystinurie","SLC3A1","SLC7A9"],"languages":["ger"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121016%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121016%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121016%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/59209","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Zerres, Klaus"]},{"key":"dc:creator","label":"Author","values":["Botzenhart, Elke Maria"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2003"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-7410","info:eu-repo/semantics/altIdentifier/doi/10.18154/RWTH-CONV-121016"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Medizin","Cystinurie","SLC3A1","SLC7A9"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["ger"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/59209","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121016%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Cystinuria is a hereditary kidney stone disease which is caused by a renal tubular defect of reabsorption of cystine and the dibasic amino acids lysine, arginine and ornithine. Once the threshold of solubility is exceeded cystine precipitates and subsequently patients suffer from recurrent kidney stone formation. Stone formation and resulting complications characterize the cause of the disease. The incidence in the common population is about 1:7000. Cystinuria contributes to approximately 1% of adult nephrolithiasis and 6-8% of childhood nephrolithiasis. The disease can be subdivided biochemically on the basis of amino acid concentrations in urine of patients and their relatives into different subtypes, which are associated with specific mutations in the SLC3A1 and SLC7A9 genes. Type I cystinuria is caused by mutations in the SLC3A1 gene and follows an autosomal recessive mode of inheritance whereas non Type I cystinuria is caused by mutations in the SLC7A9 gene and exhibits an autosomal dominant mode of inheritance with variable penetrance due to elevated concentrations of amino acids in urine in heterozygotes. Double heterozygous mutations in both genes as well as an isolated form of cystinuria have also been described. The aim of this study was to determine the contribution of the known cystinuria genes SLC3A1 and SLC7A9 to early manifesting disease forms. Therefore a study population of 21 pediatric patients of 16 families and 10 unclassified patients with a history of recurrent nephrolithiasis were investigated. Mutation detection rates for the alleles typed as type I or non type one of the non related pediatric patients were 54% (6/11) for the SLC3A1 gene and 25% (2/8) for the SLC7A9 gene. The remaining 11 unclassified alleles showed 2 mutations in the SLC3A1 and 2 mutations in the SLC7A9 gene. The detection rates for the 10 unclassified patients were 55% (11/20) for the SLC3A1- and 10% (2/20) for the SLC7A9 gene. This corresponds to a mutation detection rate of 50% for the whole study population. Within this study the hitherto unknown deletion c1749_c1751del in exon 10 of the SLC3A1 gene, two point mutations (A224V and A331V), a deletion c949_c951del in exon 8 as well as the polymorphism c1328C/T in exon 11 of the SLC7A9 gene could be identified. The results of this study confirmed the crucial role of the hitherto known genes SLC3A1 and SLC7A9 in the pathogenesis of the disease. The identification of new sequence variants in both genes shows that further investigation of the coding sequences as well as the promotor and intron sequences will extend the spectrum of so far described mutations. Comparison of population specific frequencies of known polymorphisms may reveal linkage of specific haplotypes to further factors which are related to the disease. Mutation detection rates of the study population as a whole especially with regard to the pediatric patients with early manifesting disease indicate that further genes contribute to the aetiology and the course of the disease."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University III, 113 S. : Ill., graph. Darst. (2003). doi:10.18154/RWTH-CONV-121016 = Aachen, Techn. Hochsch., Diss., 2003"]},{"key":"dc:title","label":"Title","values":["Mutationsspektrum in den Genen SLC3A1 und SLC7A9 bei jugendlichen Cystinuriepatienten"]}]}],"canonical_facts":{"dc:contributor":["Zerres, Klaus"],"dc:coverage":["DE"],"dc:creator":["Botzenhart, Elke Maria"],"dc:date":["2003"],"dc:description":["Cystinuria is a hereditary kidney stone disease which is caused by a renal tubular defect of reabsorption of cystine and the dibasic amino acids lysine, arginine and ornithine. Once the threshold of solubility is exceeded cystine precipitates and subsequently patients suffer from recurrent kidney stone formation. Stone formation and resulting complications characterize the cause of the disease. The incidence in the common population is about 1:7000. Cystinuria contributes to approximately 1% of adult nephrolithiasis and 6-8% of childhood nephrolithiasis. The disease can be subdivided biochemically on the basis of amino acid concentrations in urine of patients and their relatives into different subtypes, which are associated with specific mutations in the SLC3A1 and SLC7A9 genes. Type I cystinuria is caused by mutations in the SLC3A1 gene and follows an autosomal recessive mode of inheritance whereas non Type I cystinuria is caused by mutations in the SLC7A9 gene and exhibits an autosomal dominant mode of inheritance with variable penetrance due to elevated concentrations of amino acids in urine in heterozygotes. Double heterozygous mutations in both genes as well as an isolated form of cystinuria have also been described. The aim of this study was to determine the contribution of the known cystinuria genes SLC3A1 and SLC7A9 to early manifesting disease forms. Therefore a study population of 21 pediatric patients of 16 families and 10 unclassified patients with a history of recurrent nephrolithiasis were investigated. Mutation detection rates for the alleles typed as type I or non type one of the non related pediatric patients were 54% (6/11) for the SLC3A1 gene and 25% (2/8) for the SLC7A9 gene. The remaining 11 unclassified alleles showed 2 mutations in the SLC3A1 and 2 mutations in the SLC7A9 gene. The detection rates for the 10 unclassified patients were 55% (11/20) for the SLC3A1- and 10% (2/20) for the SLC7A9 gene. This corresponds to a mutation detection rate of 50% for the whole study population. Within this study the hitherto unknown deletion c1749_c1751del in exon 10 of the SLC3A1 gene, two point mutations (A224V and A331V), a deletion c949_c951del in exon 8 as well as the polymorphism c1328C/T in exon 11 of the SLC7A9 gene could be identified. The results of this study confirmed the crucial role of the hitherto known genes SLC3A1 and SLC7A9 in the pathogenesis of the disease. The identification of new sequence variants in both genes shows that further investigation of the coding sequences as well as the promotor and intron sequences will extend the spectrum of so far described mutations. Comparison of population specific frequencies of known polymorphisms may reveal linkage of specific haplotypes to further factors which are related to the disease. Mutation detection rates of the study population as a whole especially with regard to the pediatric patients with early manifesting disease indicate that further genes contribute to the aetiology and the course of the disease."],"dc:identifier":["https://publications.rwth-aachen.de/record/59209","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-121016%22"],"dc:language":["ger"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-7410","info:eu-repo/semantics/altIdentifier/doi/10.18154/RWTH-CONV-121016"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University III, 113 S. : Ill., graph. Darst. (2003). doi:10.18154/RWTH-CONV-121016 = Aachen, Techn. Hochsch., Diss., 2003"],"dc:subject":["info:eu-repo/classification/ddc/610","Medizin","Cystinurie","SLC3A1","SLC7A9"],"dc:title":["Mutationsspektrum in den Genen SLC3A1 und SLC7A9 bei jugendlichen Cystinuriepatienten"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:42:39Z"}