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, R, de Heredia, ML, Torrecilla, C, Rousaud-Barón, F, Angerri, O, Errasti-Murugarren, E, Nunes, V
Publicada:
1 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:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Lhospitalet De Llobregat 08907, Spain
Prat, E:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Lhospitalet De Llobregat 08907, Spain
Vecino-Pérez, M:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
González, L:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Gràcia-Garcia, S:
Fundacio Puigvert, Urinary Lithiasis Lab, Barcelona 08025, Spain
San Miguel, L:
Fundacio Puigvert, Urol Serv, Barcelona 08025, Spain
Lopera, N:
Fundacio Puigvert, Urinary Lithiasis Lab, Barcelona 08025, Spain
Arias, A:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Hosp St Joan Deu, Inst Recerca St Joan Deu, Clin Biochem Dept, Esplugas de Llobregat 08950, Spain
Artuch, R:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Hosp St Joan Deu, Inst Recerca St Joan Deu, Clin Biochem Dept, Esplugas de Llobregat 08950, Spain
de Heredia, ML:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Torrecilla, C:
Hosp Univ Bellvitge, Urol Serv, Lhospitalet De Llobregat 08908, Spain
Rousaud-Barón, F:
Fundacio Puigvert, Urol Serv, Barcelona 08025, Spain
Angerri, O:
Fundacio Puigvert, Urol Serv, Barcelona 08025, Spain
Errasti-Murugarren, E:
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Lhospitalet De Llobregat 08907, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain
Nunes, V:
Inst Invest Biomed Bellvitge IDIBELL, Gene Dis & Therapy Program, Human Mol Genet Lab, Lhospitalet De Llobregat 08908, Spain
Univ Barcelona, Hlth Sci & Med Fac, Physiol Sci Dept, Genet Sect, Lhospitalet De Llobregat 08907, Spain
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