Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia

Suthesh Sivapalaratnam, Sarah K Westbury, Jonathan C Stephens, Daniel Greene, Kate Downes, Anne M Kelly, Claire Lentaigne, William J Astle, Eric G Huizinga, Paquita Nurden, Sofia Papadia, Kathelijne Peerlinck, Christopher J Penkett, David J Perry, Catherine Roughley, Ilenia Simeoni, Kathleen Stirrups, Daniel P Hart, R Campbell Tait, Andrew D MumfordMichael A Laffan, Kathleen Freson, Willem H Ouwehand, Shinji Kunishima, Ernest Turro, NIHR BioResource

Research output: Contribution to journalArticle (Academic Journal)peer-review

40 Citations (Scopus)


The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BA have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BB and macrothrombocytopenia. To strengthen our findings, we sought further cases in 2 additional collections in the United Kingdom and Japan. Across 18 families exhibiting phenotypes consistent with autosomal dominant inheritance of macrothrombocytopenia, we report on 27 affected cases carrying 1 of 9 rare variants in GP1BB.

Original languageEnglish
Pages (from-to)520-524
Number of pages5
Issue number4
Early online date14 Nov 2016
Publication statusPublished - 26 Jan 2017


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