非肌性肌球蛋白重链9基因突变相关疾病:一个家系报告

Nonmuscle myosin heavy chain 9 gene mutations related disease:A family report

目的:提高对非肌性肌球蛋白重链9基因(myosin heavy chain 9,nonmuscle,MYH9)突变相关疾病的认识。方法:报告一个MYH9相关疾病家系的临床及实验室检查资料,包括外周血和骨髓涂片的细胞形态学检查(瑞姬染色),外周血超微结构检查,流式细胞术分析血小板膜糖蛋白,应用逆转录-聚合酶链反应和直接测序的方法分析MYH9 mRNA,应用聚合酶链反应和直接测序方法分析MYH9基因。结果:患儿及其父亲均有巨大血小板、血小板减少和粒细胞内包涵体(Dhle样小体)。患儿及其父亲血小板膜糖蛋白GPIb均轻度降低。mRNA和基因组DNA分析均证实,患儿存在杂合的碱基替代突变(5797C>T),使第1933位密码子CGA转为终止密码子TGA。基因组DNA分析显示,其父亲携带有与患儿相同的突变。结论:本例患儿及其父亲具有巨大血小板、血小板减少、粒细胞内包涵体和MYH9基因点突变,MYH9相关疾病的诊断成立。

Objective： To improve the recognition of nonmuscle myosin heavy chain 9 gene （MYH9） mutations related disease. Methods： Clinical information and laboratory data of a family of MYH9-related disease was reported. Cytomorphology examination of peripheral blood and bone marrow smears were stained with Wright-Giemsa stain. Uhrastructural studies of peripheral blood were carried out. Surface expression of platelet glycoproteins was investigated by flow cytometry. The MYH9 mRNA was isolated from EBV-transformed peripheral blood leukocytes and analyzed by reverse-transcription-polymerase chain reaction （RT-PCR） and direct sequencing. Meanwhile, mutation analysis of the MYH9 gene was performed by PCR and direct sequencing. Results： Both the patient and his father had large platelets, thrombocytopenia and characteristic granulocyte inclusion bodies （Dohle-like bodies）. Platelet glycoproteins （GPIb） of the patient and his father were also slightly lower than normal. In the patient, a heterozygous mutation （5797C 〉 T） in the MYH9 gene was detected both at the RNA level and the genomic DNA level. His father carried the same mutation. Conclusion： Patient and his father both had giant platelets, thrombocytopenia, leukocyte inclusions and mutation of MYH9. The diagnosis of MYH9-related disease was established.