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: H Kashiwagi, Y Tomiyama, S Nozaki, T Kiyoi, S Tadokoro, K Matsumoto, S Honda, S Kosugi, Y Kurata, Y Matsuzawa
• Journal: Human genetics (Hum Genet) Vol. 108 Issue 6 Pg. 459-66 (Jun 2001) ISSN: 0340-6717 [Print] Germany
• PMID: 11499670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD36 Antigens
• Luminescent Proteins
• RNA, Messenger
• Recombinant Fusion Proteins
• Green Fluorescent Proteins
• DNA

Topics

• Alleles
• Amino Acid Sequence
• Base Sequence
• CD36 Antigens (genetics, metabolism)
• Cell Line
• DNA (chemistry, genetics)
• DNA Mutational Analysis
• Female
• Gene Frequency
• Green Fluorescent Proteins
• Humans
• Japan
• Luminescent Proteins (genetics, metabolism)
• Male
• Microscopy, Fluorescence
• Mutagenesis, Insertional
• Mutation
• RNA, Messenger (genetics, metabolism)
• Recombinant Fusion Proteins (genetics, metabolism)
• Sequence Deletion
• Tumor Cells, Cultured