Similarity in joint and mucous bleeding syndromes in type 2N von Willebrand disease and severe hemophilia A coexisting with type 1 von Willebrand disease in two Chinese pedigrees.
Blood Cells Mol Dis
; 52(4): 181-5, 2014 Apr.
Article
in En
| MEDLINE
| ID: mdl-24351655
ABSTRACT
In this study, we investigated the molecular basis of two unrelated Chinese patients with hemostatic disorders. The proband of the first family had severe hemophilia A (HA) coexisting with type 1 von Willebrand disease (VWD) and the proband of the second family had type 2N VWD. Both probands had similar phenotypes, which included joint and mucosal bleeding, very low factor VIII (FVIII) activity (FVIIIC), and moderate reductions in VWF antigen (VWFAg) and VWF ristocetin cofactor activity (VWFRco), as well as a normal multimeric pattern. One FVIII mutation and three VWF mutations were identified FVIII p.R446* and VWF heterozygous p.E216K mutations were detected in proband 1 and compound heterozygosity of VWF mutations (p.R816W and c.1911delC) in proband 2. Transient expression studies in HEK293T cells proved that R816W mutation abolished the binding of FVIII to VWF and slightly impaired protein synthesis and secretion; 1911delC mutation mainly impaired VWF protein synthesis and secretion. These results provided insight into the possible pathogenic mechanism of type 2N VWD in Chinese patients carrying these mutations.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Von Willebrand Disease, Type 1
/
Von Willebrand Disease, Type 2
/
Hemophilia A
/
Hemorrhage
/
Mucous Membrane
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limits:
Adult
/
Child, preschool
/
Female
/
Humans
/
Male
Language:
En
Journal:
Blood Cells Mol Dis
Journal subject:
HEMATOLOGIA
Year:
2014
Document type:
Article