Exploring the transcriptomic variation caused by the Finnish founder mutation of lysinuric protein intolerance (LPI).

Abstract

Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by mutations in cationic amino acid transporter gene SLC7A7. Although all Finnish patients share the same homozygous mutation, their clinical manifestations vary greatly. The symptoms range from failure to thrive, protein aversion, anemia and hyperammonaemia, to immunological abnormalities, nephropathy and pulmonary alveolar proteinosis. To unravel the molecular mechanisms behind those symptoms not explained directly by the primary mutation, gene expression profiles of LPI patients were studied using genome-wide microarray technology. As a result, we discovered 926 differentially-expressed genes, including cationic and neutral amino acid transporters. The functional annotation analysis revealed a significant accumulation of such biological processes as inflammatory response, immune system processes and apoptosis. We conclude that changes in the expression of genes other than SLC7A7 may be linked to the various symptoms of LPI, indicating a complex interplay between amino acid transporters and various cellular processes.

• Authors: Maaria Tringham, Johanna Kurko, Laura Tanner, Johannes Tuikkala, Olli S Nevalainen, Harri Niinikoski, Kirsti Näntö-Salonen, Marja Hietala, Olli Simell, Juha Mykkänen
• Journal: Molecular genetics and metabolism (Mol Genet Metab) Vol. 105 Issue 3 Pg. 408-15 (Mar 2012) ISSN: 1096-7206 [Electronic] United States
• PMID: 22221392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Amino Acid Transport System y+L
• Cationic Amino Acid Transporter 1
• Fusion Regulatory Protein 1, Light Chains
• SLC7A7 protein, human
• Arginine
• Ornithine
• Lysine

Topics

• Adolescent
• Adult
• Amino Acid Metabolism, Inborn Errors (genetics, metabolism)
• Amino Acid Transport System y+L
• Arginine (blood)
• Cationic Amino Acid Transporter 1 (genetics, metabolism)
• Child
• Female
• Finland
• Founder Effect
• Fusion Regulatory Protein 1, Light Chains (genetics, metabolism)
• Gene Expression Profiling
• Humans
• Lysine (blood, urine)
• Male
• Middle Aged
• Molecular Sequence Annotation
• Molecular Sequence Data
• Mutation
• Oligonucleotide Array Sequence Analysis
• Ornithine (blood)
• Sequence Analysis, RNA
• Transcriptome
• Young Adult