Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study

Exploring the Contribution of the Transporter AGT1/rBAT in Cystinuria Progression: Insights from Mouse Models and a Retrospective Cohort Study

More than 20 years have passed since the identification of <i>SLC3A1</i> and <i>SLC7A9</i> as causative genes for cystinuria. However, cystinuria patients exhibit significant variability in the age of lithiasis onset, recurrence, and response to treatment, suggesting the pres...

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Bibliographic Details
Main Authors: Clara Mayayo-Vallverdú, Esther Prat, Marta Vecino-Pérez, Laura González, Silvia Gràcia-Garcia, Luz San Miguel, Noelia Lopera, Angela Arias, Rafael Artuch, Miguel López de Heredia, Carlos Torrecilla, Ferran Rousaud-Barón, Oriol Angerri, Ekaitz Errasti-Murugarren, Virginia Nunes
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:International Journal of Molecular Sciences
Subjects:
cystinuria
cystine transporter
rare disease
<i>SLC7A13</i> variants
functional analysis
Online Access:https://www.mdpi.com/1422-0067/24/24/17140
Description
Summary:More than 20 years have passed since the identification of <i>SLC3A1</i> and <i>SLC7A9</i> 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 <i>SLC7A13</i> 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 <i>SLC7A13</i> 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 <i>SLC7A13</i> 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.
ISSN:1661-6596
1422-0067

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