Haplotypes analysis reveals the genetic basis of type I CD36 deficiency

CD36, also known as glycoprotein IV, is classified into two distinct subgroups based on the presence or absence of its expression on monocytes. The CD36 gene spans approximately 50,000 base pairs. Historically, research has focused on identifying CD36 mutations through Sanger sequencing and next-generation sequencing (NGS), with limited exploration of haplotypes. In this study, we collected blood samples from donors with type I and type II CD36 deficiencies as well as from healthy controls, and employed single-molecule long-read sequencing (also known as Third-Generation Sequencing) of genomic DNA to analyze the genetic basis of CD36. The study identified 180 genetic variants, 12 of which were found to alter the amino acid sequence. Notably, four of these mutations (c.220 C > T; c.329_330delAC; c.430-1 G > C; c.1006 + 2 T > G) are premature termination mutations that lead to protein truncation. Using Fisher's exact test, we statistically analyzed a specific haplotype, c.-132A > C and c.329_330delAC, along with their clinical phenotypes, revealing a strong association between these variants in the 5' block and type I CD36 deficiency. We analyzed the CD36 gene sequences in platelet donors and patients with PTR (platelet transfusion refractoriness) and FNAIT (fetal and neonatal alloimmune thrombocytopenia), conducting a detailed haplotype analysis associated with type I CD36 deficiency and FNAIT.