Clinical, biochemical and molecular characterization of Cystinuria in a cohort of 12 patients

Authors

  • M Barbosa,

    Corresponding author
    1. Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, 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
      Mafalda Barbosa, Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, Praça Pedro Nunes, 88, 4099-028 Porto, Portugal
      Tel.: +351 226 070 300;
      fax: +351 226 070 399;
      e-mail: mafalda.barbosa@insa.min-saude.pt
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  • A Lopes,

    1. Unidade de Bioquímica Genética, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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  • C Mota,

    1. Serviço de Nefrologia Pediátrica
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  • E Martins,

    1. Consulta de Metabolismo, Hospital Maria Pia, Centro Hospitalar do Porto, Porto, Portugal
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  • J Oliveira,

    1. Unidade de Genética Molecular
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  • S Alves,

    1. Unidade de Investigação, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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  • P De Bonis,

    1. U.O. Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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  • M do Céu Mota,

    1. Consulta de Genética, Hospital Maria Pia, Centro Hospitalar do Porto, Porto, Portugal
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  • C Dias,

    1. Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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    • Current address: Provincial Medical Genetics Program, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

  • P Rodrigues-Santos,

    1. Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal
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  • AM Fortuna,

    1. Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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  • D Quelhas,

    1. Unidade de Bioquímica Genética, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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  • L Lacerda,

    1. Unidade de Bioquímica Genética, Centro de Genética Médica Dr. Jacinto Magalhães, Instituto Nacional de Saúde Dr. Ricardo Jorge, Porto, Portugal
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  • L Bisceglia,

    1. U.O. Genetica Medica, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
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  • ML Cardoso

    1. Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, Porto, Portugal
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Mafalda Barbosa, Unidade de Genética Médica, Centro de Genética Médica Dr. Jacinto Magalhães, Praça Pedro Nunes, 88, 4099-028 Porto, Portugal
Tel.: +351 226 070 300;
fax: +351 226 070 399;
e-mail: mafalda.barbosa@insa.min-saude.pt

Abstract

Barbosa M, Lopes A, Mota C, Martins E, Oliveira J, Alves S, De Bonis P, do Céu Mota M, Dias C, Rodrigues-Santos P, Fortuna AM, Quelhas D, Lacerda L, Bisceglia L, Cardoso ML. Clinical, biochemical and molecular characterization of Cystinuria in a cohort of 12 patients.

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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