title: Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis.
abstract: Two sisters with inherited, severe platelet dysfunction associated with P2Y(12) deficiency displayed a single base pair deletion in their P2Y(12) genes (378delC), resulting in a frame-shift and premature truncation of the protein. GL, the son of one of them, displayed mild platelet dysfunction and normal P2Y(12) sequence. We hypothesized that the abnormal platelet phenotype of GL is due to haploinsufficiency of his P2Y(12) gene. We analyzed genomic DNA from the family by Southern Blotting and real-time (RT) PCR. Southern Blotting results demonstrated that GL has a single P2Y(12) allele, inherited from his father. RT-PCR revealed that GL, his mother and aunt have one single intact P2Y(12) allele, while his father has two P2Y(12) alleles. The single GL P2Y(12) allele contains normal sequence, while his mother and aunt have the 378delC allele. The results of this study support our hypothesis and illustrate the platelet phenotype associated with P2Y(12) haploinsufficiency.
authors.affiliation: Clinica Medica, Ospedale San Paolo, Università di Milano, Via di Rudinì, 8, 20142 Milan, Italy.
authors.forename: Gessica
authors.initials: G
authors.lastname: Fontana
authors.forename: Jerry
authors.initials: J
authors.lastname: Ware
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
mesh_terms: D001791:Blood Platelet Disorders / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006238:Haploidy; D006470:Hemorrhage / Q000151:congenital / Q000235:genetics*; D006801:Humans; D008297:Male; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058925:Receptors, Purinergic P2Y12
chemical_list: C548576:P2RY12 protein, human; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12