title: Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance.
abstract: 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.
authors.affiliation: Department of Pediatrics, Akita University School of Medicine, Akita,Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shoji
authors.forename: Atsuko
authors.initials: A
authors.lastname: Noguchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Shoji
authors.forename: Mika
authors.initials: M
authors.lastname: Matsumori
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Takasago
authors.forename: Masaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Yoshino
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaji
authors.forename: Shigenori
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Akio
authors.initials: A
authors.lastname: Nakai
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
authors.forename: Youichi
authors.initials: Y
authors.lastname: Hokezu
authors.forename: Keiji
authors.initials: K
authors.lastname: Nagamatsu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mikami
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Goro
authors.initials: G
authors.lastname: Takada
mesh_terms: D000293:Adolescent; D020157:Amino Acid Transport Disorders, Inborn / Q000235:genetics* / Q000378:metabolism; D027241:Amino Acid Transport System y+L / Q000096:biosynthesis* / Q000235:genetics; D026923:Amino Acid Transport Systems, Basic / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D027201:Cationic Amino Acid Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D027301:Fusion Regulatory Protein 1, Light Chains / Q000096:biosynthesis* / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic
chemical_list: D027241:Amino Acid Transport System y+L; D026923:Amino Acid Transport Systems, Basic; D027201:Cationic Amino Acid Transporter 1; D027301:Fusion Regulatory Protein 1, Light Chains; D012333:RNA, Messenger; C469951:SLC7A6 protein, human; C421261:SLC7A7 protein, human