Faculty Collaboration Database

Hemizygosity for the gene encoding glycoprotein Ibβ is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome. J Thromb Haemost 2019 Feb;17(2):295-305

Date

12/15/2018

Pubmed ID

30549403

Pubmed Central ID

PMC6410711

DOI

10.1111/jth.14357

Scopus ID

2-s2.0-85060529568 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

Essentials How thrombocytopenia relates to bleeding in 22q11 deletion syndrome (22q11DS) is not clear. Bleeding severity, platelet count and volume, and GPIBB were examined in patients with 22q11DS. Macrothrombocytopenia and bleeding typified imperfectly overlapping subsets of 22q11DS patients. GPIBB hemizygosity does not cause macrothrombocytopenia or bleeding in patients with 22q11DS. SUMMARY: 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.

Author List

Zwifelhofer NMJ, Bercovitz RS, Weik LA, Moroi A, LaRose S, Newman PJ, Newman DK

Authors

Debra K. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Debra K. Newman PhD Investigator in the Blood Research Institute department at BloodCenter of Wisconsin

MESH terms used to index this publication - Major topics in bold

22q11 Deletion Syndrome
Adolescent
Bernard-Soulier Syndrome
Child
Child, Preschool
Female
Gene Dosage
Genetic Predisposition to Disease
Hemizygote
Hemorrhage
Hemostasis
Humans
Male
Mean Platelet Volume
Minisatellite Repeats
Phenotype
Platelet Count
Platelet Glycoprotein GPIb-IX Complex
Polymorphism, Single Nucleotide
Risk Factors
Sequence Analysis, DNA
Thrombocytopenia