Hemizygosity for the gene encoding glycoprotein Ibß is not responsible for macrothrombocytopenia and bleeding in patients with 22q11 deletion syndrome.
J Thromb Haemost
; 17(2): 295-305, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30549403
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) Ibß 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombocytopenia
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Bernard-Soulier Syndrome
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Platelet Glycoprotein GPIb-IX Complex
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22q11 Deletion Syndrome
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Hemizygote
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Hemorrhage
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Hemostasis
Type of study:
Diagnostic_studies
/
Etiology_studies
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Risk_factors_studies
Limits:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
J Thromb Haemost
Journal subject:
HEMATOLOGIA
Year:
2019
Document type:
Article
Affiliation country: