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A single nucleotide insertion in codon 317 of the CD36 gene leads to CD36 deficiency
H Kashiwagi1, Y Tomiyama, S Nozaki
1Second Department of Internal Medicine, Osaka University Medical School, Japan.
Insights
A novel CD36 gene mutation causing a frameshift and premature stop codon was identified in a Japanese subject with CD36 deficiency. This mutation, along with a previously known deletion, results in reduced CD36 mRNA levels in macrophages but absence in platelets.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- CD36 is a crucial glycoprotein receptor involved in various cellular processes, including lipid metabolism and immune response.
- CD36 deficiency, characterized by the absence of CD36 expression, can manifest in different forms, impacting platelets and immune cells.
- Two known mutations in the CD36 gene have been previously identified as causes of CD36 deficiency.
Purpose of the Study:
- To investigate the genetic basis of CD36 deficiency in a type I Japanese subject.
- To identify and characterize novel mutations responsible for CD36 deficiency.
- To elucidate the molecular mechanisms underlying CD36 deficiency in this specific case.
Main Methods:
- CD36 gene sequencing and analysis to identify mutations.
- RNase protection assays to quantify CD36 mRNA levels in macrophages and platelets.
- Genotyping to determine the allelic status of the subject.
Main Results:
- A novel single nucleotide insertion at codon 317 (nucleotide 1159) was identified, leading to a frameshift and premature stop codon.
- The subject was a compound heterozygote for this new mutation and a previously known dinucleotide deletion at nucleotide 539.
- Both mutations significantly reduced CD36 mRNA levels in macrophages, but the new mutation specifically resulted in the absence of detectable CD36 mRNA in platelets.
Conclusions:
- A new mutation in the CD36 gene contributes to CD36 deficiency, specifically impacting platelet CD36 expression.
- The findings highlight the complex genetic landscape of CD36 deficiency and its differential effects on various cell types.
- This study provides crucial insights into the molecular mechanisms underlying CD36 deficiency, aiding in understanding its clinical implications.
Abstract:
CD36 is a multifunctional integral-membrane glycoprotein that acts as a receptor for thrombospondin, collagen, long-chain fatty acids, and oxidized LDL. Platelet CD36 deficiency can be divided into two groups. In type I, neither platelets nor monocytes/macrophages express CD36; in type II, monocytes/macrophages express CD36 but platelets do not. Two known mutations cause CD36 deficiency, ie, a 478C-->T substitution in codon 90 (proline90-->serine) and a dinucleotide deletion at nucleotide 539 in codon 110. In this study we investigated a type I Japanese subject (A.T.) and identified a new mutation, a single nucleotide insertion at nucleotide 1159 in codon 317. This mutation leads to a frameshift and the appearance of a premature stop codon. CD36 gene analysis indicated that A.T. was a compound heterozygote for a dinucleotide deletion at nucleotide 539 and the single nucleotide insertion at nucleotide 1159. RNase protection studies suggested that the new mutation as well as the dinucleotide deletion led to a marked reduction in the level of CD36 mRNA in her macrophages. However, the new mutation could be detected in macrophage but not platelet CD36 mRNA. These data suggest that the allele having the single nucleotide insertion in this subject has an additional abnormality that results in the absence of the mutated CD36 mRNA in platelets.