Genetic and molecular study of cystinuria in the Valencian Community, Spain

BACKGROUND: The aim of this study has been to know the prevalence of the fo ur most common mutations reported in SLC3A1 gene involved in human cystinur ia, and to estimate the association with different phenotypic manifestation s of this disease in population of the Valencian Community, Spain. PATIENTS ANO METHODS: We have carried out a cross-sectional study with a co ntrol group in 16 families with one or more members diagnosed as cystinuric patients. 149 subjects (38 cystinuric patients, 39 relatives and 72 contro ls) were studied. Genetic analyses were carried out using PCR (polymerase c hain reaction), RFLPs (restriction fragment lenght polymorphisms) and seque ncing of PCR products. Parametric and non parametric tests were applied in the statistical analyses. RESULTS: None of the four mutations studied were found in the central group . M467T mutation was the mast prevalent in cystinuric patients as well as i n relatives, showing and allelic frequency of 0.06 and 0.03 respectively. R egarding to the association analysis between genotype and phenotype, we fou nd that, in cystinuric subjects, urinary excretion of some dibasic aminoaci d was higher in those who carried M467T mutation (p < 0.05). The formation of cystine crystals was also higher in cystinuric patients who carried this mutation (p < 0.05). CONCLUSIONS: Prevalences of recurrent mutations reported up to now in SLC3A 1 gene are very low in cystinuric subjects of the Valencian Community, Spai n. Only mutation M467T has been found, without differences between cystinur ic and their relatives, although in the first ones was associated with a mo re accurate phenotype manifestation of the disease.