Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome)
Mutations in the NMMHC-A gene cause autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly/Sebastian syndrome)
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DOI：
10.1182/blood.v97.4.1147
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发表时间：
2001-02-15
期刊：
影响因子：
20.3
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Kunishima, S;Kojima, T;Saito, H
巨血小板减少症伴白细胞夹杂物是一种罕见的常染色体显性血小板疾病，其特征为巨血小板、血小板减少症和特征性Dohle小体样白细胞夹杂物三联征。先前的一项研究通过全基因组连锁分析在染色体22q12.3-q13.2上定位了该疾病的位点。此外，人类22号染色体的完整DNA序列允许一个位置候选方法，这里的结果表明，编码非肌肉肌球蛋白重链-a的基因，NMMHC-A，在这种疾病中发生突变。研究的7个日本家庭中有6个发现了突变：3个错义突变、1个无义突变和1个碱基缺失导致过早终止。免疫荧光研究表明，中性粒细胞中的NMMHC-A分布似乎模拟了包涵体。这些结果为异常NMMHC-A参与白细胞包涵体的形成和血小板形态发生提供了证据。
Macrothrombocytopenia with leukocyte inclusions is a rare autosomal dominant platelet disorder characterized by a triad of giant platelets, thrombocytopenia, and characteristic Dohle body-like leukocyte inclusions. A previous study mapped a locus for the disease on chromosome 22q12.3-q13.2 by genome-wide linkage analysis. In addition, the complete DNA sequence of human chromosome 22 allowed a positional candidate approach, and results here indicate that the gene encoding nonmuscle myosin heavy chain-a, NMMHC-A, is mutated in this disorder. Mutations were found in 6 of 7 Japanese families studied: 3 missense mutations, a nonsense mutation, and a one-base deletion resulting in a premature termination, Immunofluorescence studies revealed that NMMHC-A distribution in neutrophils appeared to mimic the inclusion bodies. These results provide evidence for the involvement of abnormal NMMHC-A in the formation of leukocyte inclusions and also in platelet morphogenesis.