Abstract:
: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.
journal_name
Bloodjournal_title
Bloodauthors
Sivapalaratnam S,Westbury SK,Stephens JC,Greene D,Downes K,Kelly AM,Lentaigne C,Astle WJ,Huizinga EG,Nurden P,Papadia S,Peerlinck K,Penkett CJ,Perry DJ,Roughley C,Simeoni I,Stirrups K,Hart DP,Tait RC,Mumford AD,NIdoi
10.1182/blood-2016-08-732248subject
Has Abstractpub_date
2017-01-26 00:00:00pages
520-524issue
4eissn
0006-4971issn
1528-0020pii
blood-2016-08-732248journal_volume
129pub_type
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