title: Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man.
abstract: To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 839-841, and 5 bp, AAAAC, were inserted at the same position (839-841del-->insAAAAC). Mutation 839-841del-->insAAAAC led to a frameshift and appearance of a premature stop codon; it was also accompanied with a marked reduction in the amount of CD36 mRNA. The other was a 12-bp deletion at nt 1438-1449 (1438-1449del) accompanied with or without skipping of exon 9 (nt 959-1028). Mutation 1438-1449del led to an inframe 4-amino-acid deletion, whereas exon 9 skipping led to a frameshift and the appearance of a premature stop codon. Expression assay revealed that both 1438-1449del and exon 9 skipping directly caused impairment of the surface expression of CD36. A survey of the five known mutations including 839-841del-->insAAAAC and 1438-1449del in type I CD36-deficient subjects demonstrated that the five mutations covered more than 90% of genetic defects among them and that the substitution of T for C at nt 478 (478C-->T) was the most common mutation with more than 50% frequency. However, none of the four subjects that possessed isoantibodies against CD36 had 478C-->T, suggesting that 478C-->T prevents the production of isoantibodies against CD36.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan. kashi@hp-blood.med.osaka-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kashiwagi
authors.forename: Y
authors.initials: Y
authors.lastname: Tomiyama
authors.forename: S
authors.initials: S
authors.lastname: Nozaki
authors.forename: T
authors.initials: T
authors.lastname: Kiyoi
authors.forename: S
authors.initials: S
authors.lastname: Tadokoro
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Honda
authors.forename: S
authors.initials: S
authors.lastname: Kosugi
authors.forename: Y
authors.initials: Y
authors.lastname: Kurata
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D049452:Green Fluorescent Proteins; D006801:Humans; D007564:Japan; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D016254:Mutagenesis, Insertional; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
chemical_list: D018955:CD36 Antigens; D008164:Luminescent Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D004247:DNA