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Immune thrombocytopenic purpura is an acquired autoimmune disorder that is the most common cause of thrombocytopenia in children. The endocannabinoid system is involved in immune regulation. We evaluated a common missense variant (CAA/CGG; Q63R) of the gene encoding the cannabinoid receptor type 2 (GeneID 1269) in 190 children with immune thrombocytopenic purpura and 600 healthy controls. The allelic frequencies and genotype distribution of the polymorphism in the patients were significant compared to control samples (P=0.006 and P=0.0001, respectively). Interestingly, when acute and chronic immune thrombocytopenic purpura patients were analyzed separately with respect to controls, a significant overrepresentation of the RR genotype and of the R allele was observed only for the chronic form (P=0.00021 and P=0.011, respectively). The relative odds ratio suggested the risk of developing chronic form was more than double in immune thrombocytopenic purpura children homozygous for the variant (odds ratio=2.349, 95% CI: 1.544-3.573; P<0.001).

We describe a beta-spectrin variant, named beta-spectrin Bari, characterized by a truncated chain and associated with hereditary spherocytosis. The clinical phenotype consists of a moderately severe hemolytic anemia, splenomegaly, and spherocytes and acanthocytes in the blood smear. The occurrence of the truncated protein, that represents about 8% of the total beta-spectrin occurring on the membrane, results in a marked spectrin deficiency. The altered protein is due to a single point mutation at position -2 (A->G) of the acceptor splice site of intron 16 leading to an aberrant beta-spectrin message skipping exons 16 and 17 indistinguishable from that reported for beta-spectrin Winston-Salem. We provide evidence that the mutated gene is transcribed but its mRNA is less abundant than either its normal counterpart or beta-spectrin Winston-Salem mRNA. Our findings are an example of how mutations in different splice sites, although causing the same truncating effect, result in clearly different clinical pictures.