title: Molecular genetic analysis of SLC3A1 and SLC7A9 genes in Czech and Slovak cystinuric patients.
abstract: Cystinuria is a frequently inherited metabolic disorder in the Czech population (frequency 1/5,600) caused by a defect in the renal transport of cystine and dibasic amino acids (arginine, lysine and ornithine). The disease is characterized by increased urinary excretion of the amino acids and often leads to recurrent nephrolithiasis. Cystinuria is classified into two subtypes (type I and type non-I). Type I is caused predominantly by mutations in the SLC3A1 gene (2p16.3), encoding heavy subunit (rBAT) of the heterodimeric transporter. Cystinuria non-I type is caused by mutations in the SLC7A9 gene (19q13.1). In this study, we present results of molecular genetic analysis of the SLC3A1 and the SLC7A9 genes in 24 unrelated cystinuria families. Individual exons of the SLC3A1 and SLC7A9 genes were analyzed by direct sequencing. We found ten different mutations in the SLC3A1 gene including six novel ones: three missense mutations (G140R), D179Y and R365P), one splice site mutation (1137-2A>G), one deletion (1515_1516delAA), and one nonsense mutation (Q119X). The most frequent mutation, M467T; was detected in 36% of all type I classified alleles. In the SLC7A9 gene we found six mutations including three new ones: one missense mutation (G319R), one insertion (611_612insA) and one deletion (205_206delTG). One patient was compound heterozygote for one SLC3A1 and one SLC7A9 mutation. Our results confirm that cystinuria is a heterogeneous disorder at the molecular level, and contribute to the understanding of the distribution and frequency of mutations causing cystinuria in the Caucasian population.
authors.affiliation: Laboratory of Inhented Metabolic Disorders, Department of Clinical Chemistry, Palacký University and Hospital, Olomouc, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Skopková
authors.forename: Eva
authors.initials: E
authors.lastname: Hrabincová
authors.forename: Sylvie
authors.initials: S
authors.lastname: Stástná
authors.forename: Libor
authors.initials: L
authors.lastname: Kozák
authors.forename: Tomás
authors.initials: T
authors.lastname: Adam
mesh_terms: D000293:Adolescent; D000328:Adult; D017398:Alternative Splicing; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D003555:Cystinuria / Q000235:genetics*; D018153:Czech Republic; D004252:DNA Mutational Analysis; D019281:Dimerization; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018154:Slovakia
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; D018389:Codon, Nonsense; C489857:SLC3A1 protein, human; C499489:SLC7A9 protein, human