Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT

Lídia Feliubadaló, Mariona Font, Jesús Purroy, Ferran Rousaud, Xavier P. Estivill, Virginia Nunes, Eliahu Golomb, Michael Centola, Ivona Aksentijevich, Yitshak Kreiss, Boleslaw Goldman, Mordechai Pras, Daniel L. Kastner, Elon Pras, Paolo Gasparini, Luigi Bisceglia, Ercole Beccia, Michele Gallucci, Luisa De Sanctis, Alberto PonzoneGian Franco Rizzoni, Leopoldo Zelante, Maria Teresa Bassi, Alfred L. George, Marta Manzoni, Alessandro De Grandi, Mirko Riboni, John K. Endsley, Andrea Ballabio, Giuseppe Borsani, Núria Reig, Esperanza Fernández, Raúl Estévez, Marta Pineda, David Torrents, Marta Camps, Jorge Lloberas, Antonio Zorzano, Manuel Palacin

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Abstract

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref, 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (refs 3,4). We have identified a new transcript, encoding a protein (b(o,+)AT, for b(o,+) amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co- transfection of b(o,+)AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b(o,+)AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that b(o,+)AT is the light subunit of rBAT.

Original languageEnglish
Pages (from-to)52-57
Number of pages6
JournalNature Genetics
Volume23
Issue number1
DOIs
Publication statusPublished - Sep 1999
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Feliubadaló, L., Font, M., Purroy, J., Rousaud, F., Estivill, X. P., Nunes, V., Golomb, E., Centola, M., Aksentijevich, I., Kreiss, Y., Goldman, B., Pras, M., Kastner, D. L., Pras, E., Gasparini, P., Bisceglia, L., Beccia, E., Gallucci, M., De Sanctis, L., ... Palacin, M. (1999). Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT. Nature Genetics, 23(1), 52-57. https://doi.org/10.1038/12652