Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly
Mutation of MYH9, encoding non-muscle myosin heavy chain A, in May-Hegglin anomaly
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DOI：
10.1038/79069
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发表时间：
2000-09-01
期刊：
影响因子：
30.8
通讯作者：
Korczak, JF
中科院分区：
文献类型：
--
作者：
Kelley, MJ;Jawien, W;Korczak, JF
May-Hegglin异常（1，2）（MHA）是一种以血小板减少为特征的常染色体显性遗传性巨血小板减少症，其发病机制尚不清楚。巨大血小板和白细胞夹杂物研究表明，血小板的结构和功能是正常的（3-7）。提示巨核细胞碎裂缺陷（5）。这种疾病与染色体22 q12 -13有关。在这里，我们筛选在这个区域的候选基因，编码非肌肉肌球蛋白重链A（MYH 9）。十个家庭的突变在每个家族中，我们确定了与疾病状态共分离的α-螺旋卷曲螺旋或尾片段结构域内的三种序列变体之一。E1841 K突变在5个家系中发现，发生在杆结构域的保守位点。在40名正常人中未发现该突变。四个家庭有一个无意义的突变，导致截断的大部分尾部。一个家庭有一个T1155 I突变存在于受影响的母亲和女儿，但没有在母亲的父母，因此代表一个新的突变。在30个受影响的人中。在10个家系中21名健康个体和13名配偶中，MYH 9基因的一个变异与MHA的存在相关。MYH 9作为MHA疾病基因的鉴定确立了该疾病的发病机制，应该提供对正常血小板形成过程的进一步了解，并可能有助于鉴定相关疾病的遗传基础。
May-Hegglin anomaly(1,2) (MHA) is an autosomal dominant macrothrombocytopenia of unclear pathogenesis characterized by thrombocytopenia. giant platelets and leukocyte inclusions. Studies have indicated that platelet structure and function are normal(3-7). suggesting a defect in megakaryocyte fragmentations(5). The disorder has been linked to chromosome 22q12-13. Here we screen a candidate gene in this region, encoding nonmuscle myosin heavy chain A (MYH9). for mutations in ten families. In each family, we identified one of three sequence variants within either the alpha-helical coiled coil or the tailpiece domain that co-segregated with disease status. The E1841K mutation was found in 5 families and occurs at a conserved site in the rod domain. This mutation was not found in 40 normal individuals. Four families had a nonsense mutation that resulted in truncation of most of the tailpiece. One family had a T1155I mutation present in an affected mother and daughter, but not in the mother's parents, thus representing a new mutation. Among the 30 affected individuals. 21 unaffected individuals and 13 spouses in the 10 families, there was correlation of a variant of MYH9 with the presence of MHA. The identification of MYH9 as the disease gene for MHA establishes the pathogenesis of the disorder, should provide further insight into the processes of normal platelet formation and may facilitate identification of the genetic basis of related disorders.