VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population
VWF mutations and new sequence variations identified in healthy controls are more frequent in the African-American population
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DOI：
10.1182/blood-2011-10-384610
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发表时间：
2012-03-01
期刊：
影响因子：
20.3
通讯作者：
Montgomery, Robert R.
中科院分区：
文献类型：
--
作者：
Bellissimo, Daniel B.;Christopherson, Pamela A.;Montgomery, Robert R.
VWF基因的分子分析有助于VWD的诊断和分类。由于VWF基因多态性尚未完全确定，我们对184名无出血史的健康对照组进行了VWF实验室检测和基因测序。对照包括66名非裔美国人(35.9%)。我们发现了21个新的序列变异，其中13个(62%)只发生在AA中，2个(G967D，T2666M)在10%-15%的AA样本中发现，这表明它们是多态的。我们鉴定了14个以前报道的VWF突变，其中大部分是1型突变。这些对照的VWF抗原水平在正常范围内，这表明这些序列变异可能并不总是降低血浆VWF水平。AAS中发现11个突变，其中M740I、H817Q和R2185Q的突变频率为15%~18%。10名AA对照组有2N突变H817Q，1名为纯合子。该组因子的平均水平为99IU/dL，提示这种变异可能很少或没有临床症状。这项研究强调了对健康对照进行测序的重要性，以了解种族特有的序列变异，以便无症状的序列变异不会被误认为其他民族或种族群体的突变。(血。2012年；119(9)：2135-2140)
Diagnosis and classification of VWD is aided by molecular analysis of the VWF gene. Because VWF polymorphisms have not been fully characterized, we performed VWF laboratory testing and gene sequencing of 184 healthy controls with a negative bleeding history. The controls included 66 (35.9%) African Americans (AAs). We identified 21 new sequence variations, 13 (62%) of which occurred exclusively in AAs and 2 (G967D, T2666M) that were found in 10%-15% of the AA samples, suggesting they are polymorphisms. We identified 14 sequence variations reported previously as VWF mutations, the majority of which were type 1 mutations. These controls had VWF Ag levels within the normal range, suggesting that these sequence variations might not always reduce plasma VWF levels. Eleven mutations were found in AAs, and the frequency of M740I, H817Q, and R2185Q was 15%-18%. Ten AA controls had the 2N mutation H817Q; 1 was ho-mozygous. The average factor VIII level in this group was 99 IU/dL, suggesting that this variation may confer little or no clinical symptoms. This study emphasizes the importance of sequencing healthy controls to understand ethnic-specific sequence variations so that asymptomatic sequence variations are not misidentified as mutations in other ethnic or racial groups. (Blood. 2012; 119(9):2135-2140)