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Identification of the integrin β3 L718P mutation in a pedigree with autosomal dominant thrombocytopenia with anisocytosis
Author(s) -
Kobayashi Yoshiyuki,
Matsui Hirotaka,
Kanai Akinori,
Tsumura Miyuki,
Okada Satoshi,
Miki Mizuka,
Nakamura Kazuhiro,
Kunishima Shinji,
Inaba Toshiya,
Kobayashi Masao
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12160
Subject(s) - anisocytosis , mutation , chinese hamster ovary cell , integrin , haploinsufficiency , biology , genetics , phenotype , microbiology and biotechnology , medicine , gene , receptor , anemia
Summary α II bβ3 integrin mutations that result in the complete loss of expression of this molecule on the platelet surface cause Glanzmann thrombasthenia. This is usually autosomal recessive, while other mutations are known to cause dominantly inherited macrothrombocytopenia (although such cases are rare). Here, we report a 4‐generation pedigree including 10 individuals affected by dominantly inherited thrombocytopenia with anisocytosis. Six individuals, whose detailed clinical and laboratory data were available, carried a non‐synonymous ITGB 3 gene alteration resulting in mutated integrin β3 ( ITGB 3)‐L718P. This mutation causes partial activation of the α II bβ3 complex, which promotes the generation of abnormal pro‐platelet‐like protrusions through downregulating RhoA ( RHOA ) activity in transfected Chinese Hamster Ovary cells. These findings suggest a model whereby the integrin β3‐L718P mutation contributes to thrombocytopenia through gain‐of‐function mechanisms.