A Glanzmann thrombasthenia family associated with a TUBB1-related macrothrombocytopenia.
J Thromb Haemost
; 17(12): 2211-2215, 2019 12.
Article
in En
| MEDLINE
| ID: mdl-31565851
ABSTRACT
BACKGROUND:
Macrothrombocytopenia (MTP) is a rare but enigmatic complication of Glanzmann thrombasthenia (GT), an inherited bleeding disorder caused by the absence of platelet aggregation due to deficiencies of the αIIbß3 integrin.OBJECTIVES:
We report a family with type I GT and a prolonged bleeding time but unusually associated with congenital mild thrombocytopenia and platelet size heterogeneity with giant forms. METHODS ANDRESULTS:
Sanger sequencing of DNA from the propositus identified 2 heterozygous ITGB3 gene mutations p.P189S and p.C210S both of which prevent αIIbß3 expression and are causative of GT but without explaining the presence of enlarged platelets. High-throughput screening led to the detection of a predicted disease-causing heterozygous mutation in the TUBB1 gene p.G146R, encoding ß1-tubulin, a component of the platelet cytoskeleton and a gene where mutations are a known cause of MTP.CONCLUSIONS:
Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombocytopenia
/
Tubulin
/
Blood Platelets
/
Thrombasthenia
/
Integrin beta3
/
Hemostasis
/
Mutation
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
J Thromb Haemost
Journal subject:
HEMATOLOGIA
Year:
2019
Document type:
Article
Affiliation country: