SLC7A7 mutations cause lysinuric protein intolerance (LPI), an inherited multisystem disease characterized by low plasma levels of arginine and lysine, protein-rich food intolerance, failure to thrive, hepatosplenomegaly, osteoporosis, lung involvement, kidney failure, haematologic and immunological disorders.
However, the underlying pathological mechanism is unknown, and, in this analysis, we investigate the impact of point mutation in y+LAT-1's interaction with 4F2 cell-surface antigen heavy chain in causing LPI.
LPI was diagnosed by the detection of a homozygous mutation of c.713 C>T (p.Ser238Phe) in SLC7A7, which was eventually found to co-occur with UPD14mat.
The different effect of y+LAT1 mutation on arginine transport in monocytes and lymphoblasts is supposed to be due to the different expression of SLC7A7 mRNA in the two models, supporting the hypothesis that the impact of LPI defect largely depends on the relative abundance of LPI target gene in each cell type.
Lysinuric protein intolerance (LPI) is a recessively inherited aminoaciduria caused by mutations of SLC7A7, the gene encoding y+LAT1 light chain of system y<sup>+</sup>L for cationic amino acid transport.
Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter.
Lysinuric protein intolerance (LPI) is a rare metabolic disease resulting from recessive-inherited mutations in the SLC7A7 gene encoding the cationic amino-acids transporter subunit y<sup>+</sup>LAT1.
In the present study, genomic structure of SLC7A7 in six Turkish patients with lysinuric protein intolerance was examined in order to detect disease causing mutations by denaturing high pressure liquid chromatography and direct sequencing.
In addition, the expression rate of the LPI mutant y+LAT1 proteins was significantly lower and cellular mortality was markedly increased than that of the wild type y+LAT1 in transfected samples.
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.
Lysinuric protein intolerance (LPI) is an inherited defect of cationic amino acid (lysine, arginine and ornithine) transport at the basolateral membrane of intestinal and renal tubular cells caused by mutations in SLC7A7 encoding the y(+)LAT1 protein.
The present study investigates for the first time the expression and function of y+LAT1 in monocytes and macrophages isolated from a patient affected by LPI-associated PAP.
Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%.
LPI is caused by mutations in the SLC7A7 gene, which encodes the y(+)LAT-1 protein, the catalytic light chain subunit of a complex belonging to the heterodimeric amino acid transporter family.
The results of the present study provide further insight into the molecular pathogenesis of LPI: a putative multiheteromeric structure of both [4F2hc/y(+)LAT-1] and [4F2hc/y(+)LAT-2], and the interference between y(+)LAT-1 and y(+)LAT-2 proteins.
Mutations in system b(0,+) (rBAT-b(0,+)AT) and in system y(+)L (4F2hc-y(+)LAT1) cause the primary inherited aminoacidurias (PIAs) cystinuria and lysinuric protein intolerance, respectively.
We performed the mutation analysis in seven probands from five unrelated LPI families and identified five novel SLC7A7 mutations (p.M50K, p.T188I, p.R333M, p.Y457X, and c.499+?_629-?).
Lysinuric protein intolerance (LPI) is a disorder of dibasic amino acid transport secondary to mutation of the SLC7A7 gene characterized by renal failure, pulmonary alveolar proteinosis, lupus-like autoimmune symptoms and usually increased plasma citrulline.