title: Molecular characterization of cystinuria in south-eastern European countries.
abstract: Cystinuria is an autosomal recessive disorder caused by defective transport of cystine and dibasic amino acids in the proximal renal tubules and small intestine. So far, more than 128 mutations in SLC3A1 gene, and 93 in SLC7A9 gene have been described as a cause of cystinuria. We present a molecular characterization of the cystinuria in 47 unrelated south-east European families. The molecular methodology included direct sequencing, single strand conformational polymorphism, and restriction fragment length polymorphism. A total of 93 (94.9 %) out of 98 unrelated cystinuric chromosomes have been characterized. Mutations in SLC3A1 gene account for 64.3 % and in SLC7A9 gene for 30.6 % of the cystinuric chromosomes. Ten different mutations in SLC3A1 gene were found, and two of them were novel (C242R and L573X), while in SLC7A9 gene seven mutations were found, of which three were novel (G73R, V375I and c.1048_1051delACTC). The most common mutations in this study were T216M (24.5 %), M467T (16.3 %) and R365L (11.2 %) in SLC3A1 and G105R (21.4 %) in SLC7A9 gene. A population specificity of cystinuria mutations was observed; T216M mutation was the only mutation present among Gypsies, G105R was the most common mutation among Albanians and Macedonians, and R365L among Serbs. The results of this study allowed introduction of rapid, simple and cost-effective genetic diagnosis of cystinuria that enables an early preventive care of affected patients and a prenatal diagnosis in affected families.
authors.affiliation: Macedonian Academy of Science and Arts, Research Centre for Genetic Engineering and Biotechnology "Georgi D. Efremov", 1000, Skopje, Republic of Macedonia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Popovska-Jankovic
authors.forename: Velibor
authors.initials: V
authors.lastname: Tasic
authors.forename: Radovan
authors.initials: R
authors.lastname: Bogdanovic
authors.forename: Predrag
authors.initials: P
authors.lastname: Miljkovic
authors.forename: Emilija
authors.initials: E
authors.lastname: Golubovic
authors.forename: Alper
authors.initials: A
authors.lastname: Soylu
authors.forename: Marjan
authors.initials: M
authors.lastname: Saraga
authors.forename: Snezana
authors.initials: S
authors.lastname: Pavicevic
authors.forename: Esra
authors.initials: E
authors.lastname: Baskin
authors.forename: Ipek
authors.initials: I
authors.lastname: Akil
authors.forename: Alojz
authors.initials: A
authors.lastname: Gregoric
authors.forename: Marusia
authors.initials: M
authors.lastname: Lilova
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.forename: Emilija
authors.initials: E
authors.lastname: Sukarova Stefanovska
authors.forename: Dijana
authors.initials: D
authors.lastname: Plaseska-Karanfilska
mesh_terms: D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003555:Cystinuria / Q000175:diagnosis / Q000235:genetics*; D005060:Europe; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D026923:Amino Acid Transport Systems, Basic; D026921:Amino Acid Transport Systems, Neutral; C489857:SLC3A1 protein, human; C499489:SLC7A9 protein, human