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.
Shoji
Yutaka
Y
Department of Pediatrics, Akita University School of Medicine, Akita,Japan.
Noguchi
Atsuko
A
Shoji
Yasuko
Y
Matsumori
Mika
M
Takasago
Yuhei
Y
Takayanagi
Masaki
M
Yoshida
Yoshihiro
Y
Ihara
Kenji
K
Hara
Toshiro
T
Yamaguchi
Shuichi
S
Yoshino
Makoto
M
Kaji
Masayuki
M
Yamamoto
Shigenori
S
Nakai
Akio
A
Koizumi
Akio
A
Hokezu
Youichi
Y
Nagamatsu
Keiji
K
Mikami
Hitoshi
H
Kitajima
Isao
I
Takada
Goro
G
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
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