title: [SLC7A9 gene variation: impact of 13 frequent mutations in the etiology of cystinuria in a Spanish Mediterranean population].
abstract: OBJECTIVE
  The aim of this study was to investigate the presence of the most prevalent mutation in the SLC7A9 gene in families of the Mediterranean Spanish population and their association with clinical phenotypes.
  
  
  METHODS
  Twenty cystinuria families were studied (6 type I, 12 non type I, and 2 unknown type), including 48 cystinuria patients and 44 relatives. DNA was isolated and molecular analysis of 13 variations (P52L, N58_G79del22, G63R, G105R, T123M, V170M, A182T, V188M, c.614dupA, G259R, L283F, A316V and R333W) in the SLC7A9 gene was undertaken. Association studies between these mutations and urinary aminoacid concentrations, stones, urinary infections, colics and other clinical traits were carried out.
  
  
  RESULTS
  Of the 13 investigated mutations, the most prevalent mutation in cystinuria patients was c.614dupA (17.1%), which was found in 13 patients in heterozygous state (17.1%) and in 2 relatives, all of them belonging to 4 non type I families. Mutations G105R (9.2%), T123M (3.9%) and N58_G79del22 (2.6%) were detected only in non type I cystinuria patients. Meanwhile, a R333W carrier allele was found in a patient of a unknown family, and a G105R allele in a relative of a non type I family. No mutation was found in type I families and no patients with mutations in both SLC3A1 and SLC7A9 genes were found in any family.
  
  
  CONCLUSIONS
  Although we have not carried out the whole screening of SLC7A9 gene, the detection rate of variations in SLC7A9 gene suggests a greater impact of this gene in the etiology of cystinuria in our population than variations in the previously screened SLC3A1 gene. The wide variation of phenotypical traits in subjects of families with the same mutations suggests that further investigation of other genetic and/or environmental factors should be carried out.
authors.affiliation: Unidad de Epidemiología Genética y Molecular, Departamento de Medicina Preventiva, Facultad de Medicina, Universitat de València, Valencia, España.
authors.forename: Francesc
authors.initials: F
authors.lastname: Francés
authors.forename: Olga
authors.initials: O
authors.lastname: Portolés
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: José V
authors.initials: JV
authors.lastname: Sorlí
authors.forename: Antonio
authors.initials: A
authors.lastname: Sabater
authors.forename: Paula
authors.initials: P
authors.lastname: Carrasco
authors.forename: Marisa
authors.initials: M
authors.lastname: Guillén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D026923:Amino Acid Transport Systems, Basic / Q000235:genetics*; D002648:Child; D003555:Cystinuria / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D013030:Spain
chemical_list: D026923:Amino Acid Transport Systems, Basic; C499489:SLC7A9 protein, human