title: Functional characterization of SLC7A9 polymorphisms assumed to influence the cystinuria phenotype.
abstract: Cystinuria is a hereditary disorder of cystine and dibasic amino acid transport across the luminal membrane of renal tubules and intestine, resulting in recurrent nephrolithiasis. While mutations in the SLC3-A1 gene cause type I cystinuria, patients with non-type I cystinuria mostly carry mutations in the SLC7A9 gene. However, there is evidence that further genetic factors cause and influence the cystinuria phenotype. We recently demonstrated that specific polymorphisms in Exons 3, 4, 5 and 6 of the SLC7A9 gene show a significant different allelic distribution between cystinuria patients and controls. To determine the role of the variants in these exons we transfected COS7 cells with expression constructs containing different haplotypes. Sequencing of cDNAs derived from the resulting SLC7A9 mRNAs did not reveal any differences in expression between the minigenes of the specific haplotypes. Our findings suggest that the variants in SLC7A9 do not influence splicing behavior. Thus, the reasons for the different allelic distribution between cystinuria patients and controls remain unclear. It is conceivable that this distribution is caused by the association of certain alleles with so far undetected mutations in the gene.
authors.affiliation: Institute of Human Genetics, University Hospital, RWTH Aachen, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Brauers
authors.forename: C
authors.initials: C
authors.lastname: Schmidt
authors.forename: K
authors.initials: K
authors.lastname: Zerres
authors.forename: T
authors.initials: T
authors.lastname: Eggermann
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003555:Cystinuria / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection
chemical_list: D026923:Amino Acid Transport Systems, Basic; D018076:DNA, Complementary; D012333:RNA, Messenger; C499489:SLC7A9 protein, human