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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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.

Abstract Image

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非洲-加勒比地区血管性血友病的临床、表型和基因型特征：来自法属西印度群岛马提尼克岛的研究结果

背景：几项队列研究探讨了血管性血友病（VWD）的分子基础；很少有人关注非裔加勒比人。目的：确定居住在马提尼克岛的加勒比海非洲裔患者中VWD的基因型和表型特征。材料和方法：共纳入31个家庭，包括63名非洲加勒比地区的VWD患者。采用标准化问卷和血样对血管性血友病因子（VWF）进行生物学和分子遗传学分析。新的错义变异的影响已经被计算机研究预测。结果：患者中位年龄为53岁（范围9-99岁）。最常见的症状是月经过多（49%）、容易擦伤（44%）和拔牙后出血时间延长（42%）。15例（24%）患者存在VWF定量不足，其中13例（21%）为vwd - 1型，1例（1%）为vwd - 1C型，1例（2%）为vwd - 3型。诊断为vwd - 2型（VWF质性缺陷）45例（71%）。vwd - 2A型最常见，共36例。vwd - 2M型7例，2B型2例。3例患者（5%）由于ISTH BAT在0时导致VWF缺损的影响不确定。在63例患者中发现48种不同的VWF变异，包括4种新的变异。这些变异包括34个（71%）错义，7个（15%）同义，3个（6%）帧移，2个（4%）小缺失和2个（4%）基因转换。结论：本研究强调了生活在马提尼克岛的非裔加勒比VWD患者队列中基因型的独特分布。要点：基因型-表型相关性在非洲-加勒比地区有一个或多个VWF变异的VWD患者中进行了评估。VWD患者拔牙后月经过多、易瘀伤及出血时间延长是常见的。努力提高对VWD的认识和诊断，有助于更好地识别出血性疾病患者。

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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.