期刊
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
卷 93, 期 11, 页码 1743-1747出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.12830
关键词
glycoprotein Ib alpha; Bernard-Soulier; congenital thrombocytopenia
类别
资金
- Italian Ministry for University and Research (MIUR), Rome, Italy
- University of Padova, Italy
In Italy, a significant proportion of patients with autosomal dominant inheritance of macrothrombocytopenia have been recognized as having heterozygous Bernard-Soulier syndrome carrying the Bolzano-type defect. This condition prompted a systematic review of our outpatients with chronic isolated macrothrombocytopenia. We recognized that the affected members of two unrelated families represented a new variant of heterozygous Bernard-Soulier Syndrome with autosomal dominant inheritance. Sequencing analysis of the GPIb alpha gene revealed a novel heterozygous mutation, A169C, resulting in an N41H substitution in the protein. This aminoacid belongs to the first leucine-rich repeat of the chain. The molecular modeling suggests that the replacement of the N41 with a histidine (N41H) drastically disturbs the structure of the first portion of GPIb alpha N-terminal, directly involved in von Willebrand factor binding. As a consequence, platelet aggregation to 1.2 mg/mL of ristocetin is slightly impaired and flow cytometry reveals a reduced binding of monoclonals directed against N-terminal epitopes of the GPIb alpha.
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