A SINGLE NUCLEOTIDE INSERTION IN CODON-317 OF THE CD36 GENE LEADS TO CD36 DEFICIENCY

CD36 is a multifunctional integral-membrane glycoprotein that acts as a receptor for thrombospondin, collagen, long-chain fatty acids, and o xidized LDL. Platelet CD36 deficiency can be divided into two groups. In type I, neither platelets nor monocytes/macrophages express CD36; i n type II, monocytes/macrophages express CD36 but platelets do not. Tw o known mutations cause CD36 deficiency, ie, a C-478-->T substitution in codon 90 (proline90-->serine) and a dinucleotide deletion at nucleo tide 539 in codon 110. In this study we investigated a type I Japanese subject (A.T.) and identified a new mutation, a single nucleotide ins ertion al nucleotide 1159 in codon 317. This mutation leads to a frame shift and the appearance of a premature stop codon. CD36 gene analysis indicated that A.T. was a compound heterozygote for a dinucleotide de letion at nucleotide 539 and the single nucleotide insertion at nucleo tide 1159. RNase protection studies suggested that the new mutation as well as the dinucleotide deletion led to a marked reduction in the le vel of CD36 mRNA in her macrophages. However, the new mutation could b e detected in macrophage but not platelet CD36 mRNA. These data sugges t that the allele having the single nucleotide insertion in this subje ct has an additional abnormality that results in the absence of the mu tated CD36 mRNA in platelets.