Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS.
Blood Adv
; 5(15): 2987-3001, 2021 08 10.
Article
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| MEDLINE
| ID: mdl-34351388
ABSTRACT
Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU/IR = 57/77) and 50 were compound heterozygous (EU/IR = 43/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU/IR = 101/58 [5 shared]) were identified among the 379 affected alleles (EU/IR = 210/169), of which 48 (EU/IR = 18/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU/IR = 50/10), whereas 18 were recurrent (≥3 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Enfermedades de von Willebrand
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Enfermedad de von Willebrand Tipo 3
Tipo de estudio:
Diagnostic_studies
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Observational_studies
/
Prognostic_studies
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Blood Adv
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia