Five novel SLC7A7 variants and y+L gene‐expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance

Two distinct human light subunits of the heteromeric amino acid transporter, y+LAT‐1 coded by SLC7A7 and y+LAT‐2 coded by SLC7A6, are both known to induce transport system y+L activity. SLC7A7 has already been identified as the gene responsible for lysinuric protein intolerance (LPI). We successfully identified five novel SLC7A7 variants (S238F, S489P, 1630delC, 1673delG, and IVS3‐IVS5del9.7kb) in Japanese patients with LPI by PCR amplification and direct DNA sequencing. In addition, we performed a semi‐quantitative expression analysis of SLC7A7 and SLC7A6 in human tissue. In normal tissue, the gene‐expression ratio of SLC7A6 to SLC7A7 was high in the brain, muscle, and cultured skin fibroblasts; low in the kidneys and small intestine; and at an intermediate level in peripheral blood leukocytes, the lungs, and cultured lymphoblasts. The gene‐expression ratio of SLC7A6 to SLC7A7 in cultured lymphoblasts was significantly different between normal subjects and LPI patients with R410X and/or S238F, where the relative amount of SLC7A7 mRNA was significantly lower and the relative amount of SLC7A6 mRNA was statistically higher in affected lymphoblasts than in normal cells. Expression of SLC7A7 and SLC7A6 may thus be interrelated in cultured lymphoblasts. Hum Mutat 20:375–381, 2002. © 2002 Wiley‐Liss, Inc.