Two sisters with inherited, severe platelet dysfunction associated with P2Y12 deficiency displayed a single base pair deletion in their P2Y12 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 P2Y12 sequence. We hypothesized that the abnormal platelet phenotype of GL is due to haploinsufficiency of his P2Y12 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 P2Y12 allele, inherited from his father. RT-PCR revealed that GL, his mother and aunt have one single intact P2Y12 allele, while his father has two P2Y12 alleles. The single GL P2Y12 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 P2Y12 haploinsufficiency.

Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis / G. Fontana, J. Ware, M.N. Cattaneo. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 94:4(2009 Apr), pp. 581-584.

Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis

G. Fontana
Primo
;
M.N. Cattaneo
Ultimo
2009-04

Abstract

Two sisters with inherited, severe platelet dysfunction associated with P2Y12 deficiency displayed a single base pair deletion in their P2Y12 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 P2Y12 sequence. We hypothesized that the abnormal platelet phenotype of GL is due to haploinsufficiency of his P2Y12 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 P2Y12 allele, inherited from his father. RT-PCR revealed that GL, his mother and aunt have one single intact P2Y12 allele, while his father has two P2Y12 alleles. The single GL P2Y12 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 P2Y12 haploinsufficiency.
Congenital bleeding diathesis; Haploinsufficiency; P2y(12) gene
Settore MED/09 - Medicina Interna
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/71270
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