Kunishima S, Kojima T, Matsushita T, Tanaka T, Tsurusawa M, Furukawa Y, Nakamura Y, Okamura T, Amemiya N, Nakayama T, Kamiya T, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan.
Blood. 2001 Feb 15;97(4):1147-9. doi: 10.1182/blood.v97.4.1147.
Macrothrombocytopenia with leukocyte inclusions is a rare autosomal dominant platelet disorder characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle 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.
伴有白细胞包涵体的大血小板减少症是一种罕见的常染色体显性血小板疾病，其特征为三联征：巨大血小板、血小板减少症以及特征性的似杜勒小体的白细胞包涵体。先前的一项研究通过全基因组连锁分析将该疾病的一个基因座定位在22号染色体的q12.3 - q13.2区域。此外，人类22号染色体的完整DNA序列使得采用位置候选基因法成为可能，此处的研究结果表明，编码非肌肉肌球蛋白重链A（NMMHC - A）的基因在该疾病中发生了突变。在所研究的7个日本家族中的6个发现了突变：3个错义突变、1个无义突变以及1个导致提前终止的单碱基缺失。免疫荧光研究显示，NMMHC - A在中性粒细胞中的分布似乎与包涵体相似。这些结果为异常的NMMHC - A参与白细胞包涵体的形成以及血小板形态发生提供了证据。
