1例非肌性肌球蛋白重链9基因相关疾病家系并文献复习

Non-muscle myosin heavy chain 9 gene related disease: a pedigree report and literature review

目的鉴定1例非肌性肌球蛋白重链9(MYH9)基因相关疾病家系的致病突变。方法调查收集先证者和家系成员病史资料,观察其临床特征和实验室检查指标。采用芯片捕获高通量测序方法检测先证者MYH9基因,确定突变位点后,对先证者和家系成员进行Sanger验证。结果该家系三代4名患者均有鼻衄、瘀斑紫癜、外伤血肿或月经量增多病史,长期存在镜下血尿和蛋白尿。血涂片镜检均有血小板减少、巨大血小板和粒细胞异常包涵体“三联征”。所有患者MYH9基因第40内含子供体剪接位点存在错义突变c.5765+2T>A(p.R1922Rfs*43),且该基因突变与疾病表型共分离。结论该家系存在MYH9基因c.5765+2T>A(p.R1922Rfs*43)剪接突变,是MYH9基因相关疾病的致病突变,为国内首次报道。

Objective To identify the pathogenic mutation of MYH9(myosin heavy chain 9) gene of a pedigree affected with non-muscle myosin heavy chain 9 gene related disease. Methods Medical records of the proband and her family members were collected and investigated. The clinical features and laboratory examination indexes were analyzed. The MYH9 gene of the proband was detected by chip capture high-throughput sequencing method. Following the mutation sites were identified, the proband and all the family members were validated by Sanger sequencing. Results The 4 patients in 3 generations of this pedigree had the history of epistaxis, purpura, traumatic hematoma or increased menstrual volume and persistent microscopic hematuria and proteinuria. Their blood smear under microscopy showed the typical triad of thrombocytopenia, giant platelets, and abnormal inclusion bodies in granulocytes. The missense mutation C. 5765+2 T>A(p.R1922 Rfs*43) was found at the donor splicing site of the 40 th intron of MYH9 gene in all the patients from this family. The variant mutation has co-segregated with the phenotype in this pedigree. Conclusion The splicing mutation of MYH9 gene c.5765+2 T>A(p.R1922 Rfs*43) is present in this family and should be the the pathogenic mutation in the pedigree, which has been reported for the first time in China.