Hemizygosity for the gene encoding glycoprotein Ibβ is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome
Author(s): ,
N. M. J. Zwifelhofer
Affiliations:
Blood Research Institute, BloodCenter of Wisconsin – part of Versiti, Milwaukee, USA
,
R. S. Bercovitz
Affiliations:
Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, USA. Department of Pediatrics, Division of Hematology and Oncology, Feinberg School of Medicine, Northwestern University, Chicago, USA
,
L. A. Weik
Affiliations:
Children's Hospital of Wisconsin, Milwaukee, USA
,
A. Moroi
Affiliations:
Blood Research Institute, BloodCenter of Wisconsin – part of Versiti, Milwaukee, USA
,
S. LaRose
Affiliations:
Blood Research Institute, BloodCenter of Wisconsin – part of Versiti, Milwaukee, USA
,
P. J. Newman
Affiliations:
Blood Research Institute, BloodCenter of Wisconsin – part of Versiti, Milwaukee, USA. Department of Cell Biology, Neurobiology & Anatomy, Medical College of Wisconsin, Milwaukee, USA
Correspondence: Debra K. Newman, Blood Research Institute, Blood Center of Wisconsin – part of Versiti, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA|Tel.: +1 414 937 3820|E‐mail: debra.newman@bcw.edu
D. K. Newman
Affiliations:
Blood Research Institute, BloodCenter of Wisconsin – part of Versiti, Milwaukee, USA. Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, USA. Department of Microbiology & Immunology, Medical College of Wisconsin, Milwaukee, USA
Correspondence: Debra K. Newman, Blood Research Institute, Blood Center of Wisconsin – part of Versiti, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA|Tel.: +1 414 937 3820|E‐mail: debra.newman@bcw.edu
ISTH Academy. Newman D. Feb 8, 2019; 273378
Debra Newman
Debra Newman
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Background and objectives
Macrothrombocytopenia and bleeding are frequently associated with 22q11 deletion syndrome (22q11DS). GPIBB, which encodes the glycoprotein (GP) Ibβ subunit of GPIb–IX–V, is commonly deleted in patients with 22q11DS. Absence of functional GPIb–IX–V causes Bernard–Soulier syndrome, which is a severe bleeding disorder characterized by macrothrombocytopenia. Patients with 22q11DS are often obligate hemizygotes for GPIBB, and those with only a pathogenically disrupted copy of GPIBB present with Bernard–Soulier syndrome. The objective of this study was to determine how GPIBB hemizygosity and sequence variation relate to macrothrombocytopenia and bleeding in patients with 22q11DS who do not have Bernard‐Soulier syndrome.
Patients/methods
We thoroughly characterized bleeding severity, mean platelet volume, platelet count and GPIBB copy number and sequence in patients with 22q11DS.
Results and conclusions
Macrothrombocytopenia and mild bleeding were observed in incompletely overlapping subsets of patients, and GPIBB copy number and sequence variation did not correlate with either macrothrombocytopenia or bleeding in patients with 22q11DS. These findings indicate that GPIBB hemizygosity does not result in either macrothrombocytopenia or bleeding in these patients. Alternative genetic causes of macrothrombocytopenia, potential causes of acquired thrombocytopenia and bleeding and ways in which platelet size, platelet count and GPIBB sequence information can be used to aid in the diagnosis and management of patients with 22q11DS are discussed.
Keyword(s)
22q11 deletion syndrome, Bernard–Soulier syndrome, giant platelets, glycoprotein Ib, thrombocytopenia
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