Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients |
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| Authors: | Barbosa M Lopes A Mota C Martins E Oliveira J Alves S De Bonis P Mota M do Céu Dias C Rodrigues-Santos P Fortuna A M Quelhas D Lacerda L Bisceglia L Cardoso M L |
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| Institution: | 1. Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalh?es, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal;2. Instituto de Ciências da Vida e da Saúde (ICVS), Escola de Ciências da Saúde, Universidade do Minho, Braga, Portugal;3. Unidade de Bioquímica Genética, Centro de Genética Médica Dr. Jacinto Magalh?es, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal;4. Servi?o de Nefrologia Pediátrica;5. Consulta de Metabolismo, Hospital Maria Pia, Centro Hospitalar do Porto, Porto, Portugal;6. Unidade de Genética Molecular;7. Unidade de Investiga??o, Centro de Genética Médica Dr. Jacinto Magalh?es, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal;8. U.O. Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy;9. Consulta de Genética, Hospital Maria Pia, Centro Hospitalar do Porto, Porto, Portugal;10. Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal;11. Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal |
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| Abstract: | Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria. |
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| Keywords: | Cystinuria MLPA analysis silent mutation SLC3A1 gene SLC7A9 gene |
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