Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)
Phenotype and genotype of a cohort of families historically diagnosed with type 1 von Willebrand disease in the European study, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand Disease (MCMDM-1VWD)
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DOI：
10.1182/blood-2006-05-020784
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Peake, Ian
中科院分区：
文献类型：
--
作者：
Goodeve, Anne;Eikenboom, Jeroen;Peake, Ian
1型血管性血友病（VWD）的特征是个人和家族出血史，同时正常血浆血管性血友病因子（VWF）水平降低。对这种疾病的分子基础了解甚少。本研究的目的是确定表型和基因型及其在历史上诊断为1型VWD患者的关系。根据既往1型VWD诊断，在9个欧洲国家招募了家族。记录出血症状，分析血浆表型，并在所有指示病例（IC）中进行VWF突变分析。表型和分子分析将患者分为有或无表型提示定性VWF缺陷（异常多聚体）和有或无突变的患者。150个IC中共有105个（70%）鉴定出突变。异常多聚体的亚组（38%的IC，57/150）显示VWF基因突变的高患病率（95%的IC，54/57），而在定性正常VWF的人中，较少的突变被确定（55%的IC，51/93）。大约三分之一的I型VWD病例可以重新考虑为2型。剩下的一组可以被认为是“真正的”1型VWD，尽管只有55%的人发现了突变。
Type 1 von Willebrand disease (VWD) is characterized by a personal and family history of bleeding coincident with reduced levels of normal plasma von Willebrand factor (VWF). The molecular basis of the disorder is poorly understood. The aims of this study were to determine phenotype and genotype and their relationship in patients historically diagnosed with type 1 VWD. Families were recruited in 9 European countries based on previous type 1 VWD diagnosis. Bleeding symptoms were recorded, plasma phenotype analyzed, and VWF mutation analysis performed in all index cases (ICs). Phenotypic and molecular analysis stratified patients into those with or without phenotypes suggestive of qualitative VWF defects (abnormal multimers) and with or without mutations. A total of 105 of 150 ICs (70%) had mutations identified. A subgroup with abnormal multimers (38% of ICs, 57 of 150) showed a high prevalence of VWF gene mutations (95% of ICs, 54 of 57), whereas in those with qualitatively normal VWF, fewer mutations were identified (55% of ICs, 51 of 93). About one third of the type I VWD cases recruited could be reconsidered as type 2. The remaining group could be considered "true" type 1 VWD, although mutations were found in only 55%.