一个非肌性肌球蛋白重链9基因相关疾病家系的临床特征及基因突变分析

Clinical features and genetic analysis of a pedigree affected with non-muscle myosin heavy chain 9 gene related disease

目的鉴定一个非肌性肌球蛋白重链9基因(myosin heavy chain 9,MHY9)相关疾病家系的基因突变类型并分析其表型特点。方法对先证者及其家系成员采集外周静脉血,分别进行血常规检查,包括血小板计数和外周血瑞氏染色分析观察粒细胞包涵体和巨大血小板。用PCR扩增先证者及家系成员和正常对照者MYH9基因的第2、17、27、31、39、41外显子,直接测序法分析PCR产物的核苷酸序列,确定其突变位点。结果家系中的患者有典型的"血小板减少、巨大血小板、粒细胞包涵体"三联征,2例患者有肾炎、白内障。家系中所有患者在MYH9基因上的第39外显子第5521位核苷酸均存在杂合错义突变c.5521G>A(p.Glu1841Lys),正常对照及家系中正常成员未见此突变。结论该家系存在MYH9基因c.5521G>A(p.Glu1841Lys)突变,导致MYH9相关疾病。

Objective To identify the mutation type of MYH9 gene and investigate the clinical features of a pedigree affected with non-muscle myosin heavy chain 9 gene related disease. Methods Peripheral blood samples of the proband and his family members were collected. Routine blood tests were performed, which included platelet counting and Wright’s staining to observe granulocyte inclusions and giant platelets. PCR was used to amplify exons 2, 17, 27, 31, 39 and 41 of the MYH9 gene, and the mutation site was determined by Sanger sequencing. Results All patients from the pedigree presented a typical triad of thrombocytopenia, giant platelets, and inclusion bodies in leukocytes. In addition, two patients had nephritis and cataract. All affected members carried a heterozygous missense mutation of c. 5521G>A (p.glu1841Lys) in exon 39 of the MYH9 gene. The same mutation was not found among healthy members of the pedigree as well as the controls. Conclusion The c. 5521G>A (p.Glu1841Lys) mutation in the MYH9 gene probably underlies the MYH9-related disease in this pedigree.