A familial case of MYH9 gene mutation associated with multiple functional and structural platelet abnormalities.
A familial case of MYH9 gene mutation associated with multiple functional and structural platelet abnormalities.
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DOI：
10.1038/s41598-022-24098-5
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发表时间：
2022-11-20
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
MYH 9基因突变导致巨血小板减少症，常与血小板减少症相关。在这里，我们研究了三个家庭成员的功能和结构的血小板与杂合突变R1933 X在MYH 9基因，特征密切相关的疾病称为梅-赫格林异常和塞巴斯蒂安综合征。检查包括全血细胞计数、血涂片镜检、血小板流式细胞术（活化前后P-选择素和活性整合素αIIbβ3的表达）、血小板驱动的血凝块收缩（回缩）动力学以及血小板扫描/透射电镜。尽管有严重的血小板减少症，范围为（36-86）× 109/l，但在检查时没有患者出现血小板减少，尽管他们有月经过多、自发性瘀斑和产后出血的病史。流式细胞术显示背景血小板活化，表现为P-选择素和活性αIIbβ3整合素的过表达高于正常水平。在TRAP诱导的刺激后，先证者和她的姐姐表达P-选择素的血小板分数低于正常反应，表明部分血小板不应性。血凝块收缩开始延迟。电子显微镜下可见巨大血小板，有多个丝状伪足，α颗粒融合，有扩张的开放小管系统，含有丝状和囊泡状包涵体。这一新的概念意味着MYH 9基因中的R1933 X突变不仅与血小板减少症有关，而且与血小板的定性结构和功能缺陷有关。血小板功能障碍包括收缩性受损，这可破坏止血凝块的压实，使凝块变弱且具有渗透性，因此使MYH 9基因突变患者易患出血表型。
Mutations in the MYH9 gene result in macrothrombocytopenia often associated with hemorrhages. Here, we studied the function and structure of platelets in three family members with a heterozygous mutation R1933X in the MYH9 gene, characteristic of closely related disorders known as the May-Hegglin anomaly and Sebastian syndrome. The examination included complete blood count, blood smear microscopy, platelet flow cytometry (expression of P-selectin and active integrin αIIbβ3 before and after activation), the kinetics of platelet-driven contraction (retraction) of blood clots, as well as scanning/transmission electron microscopy of platelets. Despite severe thrombocytopenia ranging (36–86) × 109/l, none of the patients had hemorrhages at the time of examination, although they had a history of heavy menstruation, spontaneous ecchymosis, and postpartum hemorrhage. Flow cytometry showed background platelet activation, revealed by overexpression of P-selectin and active αIIbβ3 integrin above normal levels. After TRAP-induced stimulation, the fractions of platelets expressing P-selectin in the proband and her sister were below normal response, indicating partial platelet refractoriness. The initiation of clot contraction was delayed. Electron microscopy revealed giant platelets with multiple filopodia and fusion of α-granules with dilated open canalicular system, containing filamentous and vesicular inclusions. The novel concept implies that the R1933X mutation in the MYH9 gene is associated not only with thrombocytopenia, but also with qualitative structural and functional defects in platelets. Platelet dysfunction includes impaired contractility, which can disrupt the compaction of hemostatic clots, making the clots weak and permeable, therefore predisposing patients with MYH9 gene mutations to the hemorrhagic phenotype.
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血块的收缩受损在前并预测术后静脉血栓栓塞。
影响因子：
4.6
作者：
Evtugina NG;Peshkova AD;Pichugin AA;Weisel JW;Litvinov RI
通讯作者：
Litvinov RI
DOI：
10.1161/atvbaha.118.311390
发表时间：
2019-01-01
影响因子：
8.7
作者：
Nechipurenko, Dmitry Y.;Receveur, Nicolas;Panteleev, Mikhail A.
通讯作者：
Panteleev, Mikhail A.
影响因子：
3
作者：
Lim, Hui Yin;Leung, Patrick;Ho, Prahlad
通讯作者：
Ho, Prahlad
影响因子：
6
作者：
Giang Le Minh;Peshkova, Alina D.;Litvinov, Rustem I.
通讯作者：
Litvinov, Rustem I.
影响因子：
10.4
作者：
Eckly, A.;Rinckel, J. -Y.;Leon, C.
通讯作者：
Leon, C.