SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance

Giuseppe Borsani, Maria Teresa Bassi, Maria Pia Sperandeo, Alessandro De Grandi, Anna Buoninconti, Mirko Riboni, Marta Manzoni, Barbara Incerti, Antonio Pepe, Generoso Andria, Andrea Ballabio, Gianfranco Sebastio

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Abstract

Lysinuric protein intolerance (LPI, MIM 222700) is an autosomal recessive multisystem disorder found mainly in Finland and Italy. On a normal diet, LPI patients present poor feeding, vomiting, diarrhoea, episodes of hyperammoniaemic coma and failure to thrive. Hepatosplenomegaly, osteoporosis and a life-threatening pulmonary involvement (alveolar proteinosis) are also seen. LPI is caused by defective cationic amino acid (CAA) transport at the basolateral membrane of epithelial cells in kidney and intestine. Metabolic derangement is characterized by increased renal excretion of CAA, reduced CAA absorption from intestine and orotic aciduria. The gene causing LPI was assigned using linkage analysis to chromosome 14q11.2 near the T-cell receptor α/δ chains locus, and a critical region has been defined. We have identified two new transcripts (SLC7A8 and SLC7A7) homologous to amino acid transporters, highly expressed in kidney and mapping in the LPI critical region. Mutational analysis of both transcripts revealed that SLC7A7 (for solute carrier family 7, member 7) is mutated in LPI. In five Italian patients, we found either an insertion or deletion in the coding sequence, which provides evidence of a causative role of SLC7A7 in LPI. Furthermore, we detected a splice acceptor change resulting in a frameshift and premature translation termination in four unrelated Finnish patients. This mutation may represent the founder LPI allele in Finland.

Original languageEnglish
Pages (from-to)297-301
Number of pages5
JournalNature Genetics
Volume21
Issue number3
DOIs
Publication statusPublished - Mar 1999

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ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Borsani, G., Bassi, M. T., Sperandeo, M. P., De Grandi, A., Buoninconti, A., Riboni, M., Manzoni, M., Incerti, B., Pepe, A., Andria, G., Ballabio, A., & Sebastio, G. (1999). SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nature Genetics, 21(3), 297-301. https://doi.org/10.1038/6815