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

Research output: Contribution to journalArticle

241 Citations (Scopus)

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

Fingerprint

Cystinuria
Amino Acid Transport Systems
Mutation
COS Cells
Missense Mutation
Diamino Amino Acids
Light
Jews
Cystine
Hispanic Americans
Placenta
Genes
Small Intestine
Transfection
Arginine
Cell Membrane
Kidney
Amino Acids
Liver

ASJC Scopus subject areas

  • Genetics

Cite this

Feliubadaló, L., Font, M., Purroy, J., Rousaud, F., Estivill, X. P., Nunes, V., ... 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

Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT. / Feliubadaló, Lídia; Font, Mariona; Purroy, Jesús; Rousaud, Ferran; Estivill, Xavier P.; Nunes, Virginia; Golomb, Eliahu; Centola, Michael; Aksentijevich, Ivona; Kreiss, Yitshak; Goldman, Boleslaw; Pras, Mordechai; Kastner, Daniel L.; Pras, Elon; Gasparini, Paolo; Bisceglia, Luigi; Beccia, Ercole; Gallucci, Michele; De Sanctis, Luisa; Ponzone, Alberto; Rizzoni, Gian Franco; Zelante, Leopoldo; Bassi, Maria Teresa; George, Alfred L.; Manzoni, Marta; De Grandi, Alessandro; Riboni, Mirko; Endsley, John K.; Ballabio, Andrea; Borsani, Giuseppe; Reig, Núria; Fernández, Esperanza; Estévez, Raúl; Pineda, Marta; Torrents, David; Camps, Marta; Lloberas, Jorge; Zorzano, Antonio; Palacin, Manuel.

In: Nature Genetics, Vol. 23, No. 1, 09.1999, p. 52-57.

Research output: Contribution to journalArticle

Feliubadaló, L, Font, M, Purroy, J, Rousaud, F, Estivill, XP, Nunes, V, Golomb, E, Centola, M, Aksentijevich, I, Kreiss, Y, Goldman, B, Pras, M, Kastner, DL, Pras, E, Gasparini, P, Bisceglia, L, Beccia, E, Gallucci, M, De Sanctis, L, Ponzone, A, Rizzoni, GF, Zelante, L, Bassi, MT, George, AL, Manzoni, M, De Grandi, A, Riboni, M, Endsley, JK, Ballabio, A, Borsani, G, Reig, N, Fernández, E, Estévez, R, Pineda, M, Torrents, D, Camps, M, Lloberas, J, Zorzano, A & Palacin, M 1999, 'Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT', Nature Genetics, vol. 23, no. 1, pp. 52-57. https://doi.org/10.1038/12652
Feliubadaló, Lídia ; Font, Mariona ; Purroy, Jesús ; Rousaud, Ferran ; Estivill, Xavier P. ; Nunes, Virginia ; Golomb, Eliahu ; Centola, Michael ; Aksentijevich, Ivona ; Kreiss, Yitshak ; Goldman, Boleslaw ; Pras, Mordechai ; Kastner, Daniel L. ; Pras, Elon ; Gasparini, Paolo ; Bisceglia, Luigi ; Beccia, Ercole ; Gallucci, Michele ; De Sanctis, Luisa ; Ponzone, Alberto ; Rizzoni, Gian Franco ; Zelante, Leopoldo ; Bassi, Maria Teresa ; George, Alfred L. ; Manzoni, Marta ; De Grandi, Alessandro ; Riboni, Mirko ; Endsley, John K. ; Ballabio, Andrea ; Borsani, Giuseppe ; Reig, Núria ; Fernández, Esperanza ; Estévez, Raúl ; Pineda, Marta ; Torrents, David ; Camps, Marta ; Lloberas, Jorge ; Zorzano, Antonio ; Palacin, Manuel. / Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (b(o,+)AT) of rBAT. In: Nature Genetics. 1999 ; Vol. 23, No. 1. pp. 52-57.
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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.",
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AU - Purroy, Jesús

AU - Rousaud, Ferran

AU - Estivill, Xavier P.

AU - Nunes, Virginia

AU - Golomb, Eliahu

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AU - Pras, Elon

AU - Gasparini, Paolo

AU - Bisceglia, Luigi

AU - Beccia, Ercole

AU - Gallucci, Michele

AU - De Sanctis, Luisa

AU - Ponzone, Alberto

AU - Rizzoni, Gian Franco

AU - Zelante, Leopoldo

AU - Bassi, Maria Teresa

AU - George, Alfred L.

AU - Manzoni, Marta

AU - De Grandi, Alessandro

AU - Riboni, Mirko

AU - Endsley, John K.

AU - Ballabio, Andrea

AU - Borsani, Giuseppe

AU - Reig, Núria

AU - Fernández, Esperanza

AU - Estévez, Raúl

AU - Pineda, Marta

AU - Torrents, David

AU - Camps, Marta

AU - Lloberas, Jorge

AU - Zorzano, Antonio

AU - Palacin, Manuel

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