Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study
Por:
Mayayo-Vallverdú C, Prat E, Vecino-Pérez M, González L, Gràcia-Garcia S, San Miguel L, Lopera N, Arias A, Artuch-Iriberri R, López de Heredia M, Torrecilla C, Rousaud-Barón F, Angerri O, Errasti-Murugarren E and Nunes V
Publicada:
1 dic 2023
Ahead of Print:
5 dic 2023
Resumen:
More than 20 years have passed since the identification of SLC3A1 and SLC7A9 as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the presence of modulatory factors influencing cystinuria severity. In 2016, a second renal cystine transporter, AGT1, encoded by the SLC7A13 gene, was discovered. Although it was discarded as a causative gene for cystinuria, its possible effect as a modulatory gene remains unexplored. Thus, we analyzed its function in mouse models of cystinuria, screened the SLC7A13 gene in 34 patients with different lithiasic phenotypes, and functionally characterized the identified variants. Mice results showed that AGT1/rBAT may have a protective role against cystine lithiasis. In addition, among the four missense variants detected in patients, two exhibited a 25% impairment in AGT1/rBAT transport. However, no correlation between SLC7A13 genotypes and lithiasis phenotypes was observed in patients, probably because these variants were found in heterozygous states. In conclusion, our results, consistent with a previous study, suggest that AGT1/rBAT does not have a relevant effect on cystinuria patients, although an impact in patients carrying homozygous pathogenic variants cannot be discarded.
Filiaciones:
Mayayo-Vallverdú C:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain
Prat E:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain
Vecino-Pérez M:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
González L:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Gràcia-Garcia S:
Urinary Lithiasis Laboratory, Fundació Puigvert, 08025 Barcelona, Spain
San Miguel L:
Urology Service, Fundació Puigvert, 08025 Barcelona, Spain
Lopera N:
Urinary Lithiasis Laboratory, Fundació Puigvert, 08025 Barcelona, Spain
Arias A:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Clinical Biochemistry Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
Artuch-Iriberri R:
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Clinical Biochemistry Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain
López de Heredia M:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Torrecilla C:
Urology Service, Hospital Universitari de Bellvitge, 08908 L'Hospitalet de Llobregat, Spain
Rousaud-Barón F:
Urology Service, Fundació Puigvert, 08025 Barcelona, Spain
Angerri O:
Urology Service, Fundació Puigvert, 08025 Barcelona, Spain
Errasti-Murugarren E:
Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain
Nunes V:
Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), 08908 L'Hospitalet de Llobregat, Spain
Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain
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