Clinical, Phenotypic and Genotypic Characteristics of Von Willebrand Disease in Afro-Caribbeans: Results From a Study in Martinique Island, French West Indies.

IF 3 2区医学 Q2 HEMATOLOGY

Haemophilia Pub Date : 2025-03-23 DOI:10.1111/hae.70003

Marie-Daniéla Dubois, Olivier Nicolas Pierre-Louis, Serge Pierre-Louis, Pierre Boisseau, Cécile V Denis, Annabelle Dupont, Jenny Goudemand, Caterina Casari, Emmanuelle Jeanpierre, Christophe Zawadzki, Béatrice Ferrey, Johalène Rabout, Pascal Fuseau, Emelyne Chonville, Franck Michel, Marie-Nadiège Yerro, Yves Gruel, Olivier Christophe, Peter J Lenting, Eustase Janky, Sophie Susen, Rémi Neviere

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引用次数: 0

Abstract

Background: Several cohort studies have investigated the molecular basis of von Willebrand disease (VWD); very few have focused on the Afro-Caribbean population.

Objectives: To determine the genotypic and phenotypic characterization of VWD in a large cohort of Afro-Caribbean patients living in Martinique.

Materials and methods: A total of 31 families comprising 63 Afro-Caribbean patients with VWD were enrolled. A standardized questionnaire and blood samples were collected for biological and molecular genetic analyses of von Willebrand factor (VWF). The impact of new missense variants has been predicted by in silico studies.

Results: The median age of patients was 53 years (range 9-99). The most frequent symptoms were menorrhagia (49%), easy bruising (44%) and prolonged bleeding after tooth extraction (42%). Fifteen patients (24%) had quantitative deficiencies of VWF, of whom 13 (21%) were assigned as VWD-type 1, 1 (1%) as VWD-type 1C and 1 (2%) as VWD-type 3. Forty-five patients were diagnosed with VWD-type 2 (qualitative defects of VWF) (71%). VWD-type 2A was the most frequent, with 36 patients. Seven patients had VWD-type 2M and two patients had VWD-type 2B. Three patients (5%) had an indeterminate effect of the VWF defect due to ISTH BAT at 0. Forty-eight different VWF variants, including 4 novel variants, were identified in 63 patients. The variants consisted of 34 (71%) missense, 7 (15%) synonymous, 3 (6%) frameshifts, 2 (4%) small deletions and 2 (4%) gene conversions.

Conclusions: This study emphasizes the unique distribution of genotypes in our cohort of Afro-Caribbean VWD patients living in Martinique.

Essentials: Genotype-phenotype correlation was assessed in VWD Afro-Caribbean patients with one or more VWF variants. Menorrhagia, easy bruising and prolonged bleeding after tooth extraction are common in VWD patients. Efforts to increase the awareness and diagnosis of VWD have contributed to a better identification of patients with bleeding disorders.

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来源期刊

Haemophilia 医学-血液学

CiteScore

6.50

自引率

28.20%

发文量

226

审稿时长

3-6 weeks

期刊介绍： Haemophilia is an international journal dedicated to the exchange of information regarding the comprehensive care of haemophilia. The Journal contains review articles, original scientific papers and case reports related to haemophilia care, with frequent supplements. Subjects covered include: clotting factor deficiencies, both inherited and acquired: haemophilia A, B, von Willebrand''s disease, deficiencies of factor V, VII, X and XI replacement therapy for clotting factor deficiencies component therapy in the developing world transfusion transmitted disease haemophilia care and paediatrics, orthopaedics, gynaecology and obstetrics nursing laboratory diagnosis carrier detection psycho-social concerns economic issues audit inherited platelet disorders.