深圳市卫生计生系统科研项目(SZFZ2018054);深圳市科技研发资金(JCYJ20180228175408411)
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?mus? cle 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 mi? croscopy showed the typical triad of thrombocytopenia, giant platelets, and abnormal inclusion bodies in granulocytes. The missense mutation C. 5765+2T>A (p.R1922Rfs? 43) was found at the donor splicing site of the 40th 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+2T>A (p.R1922Rfs? 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.
罗小娟,曹科,陈诗杨,付笑迎,毛晓宁,张艳,李长钢,陈运生.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[J].临床检验杂志,2021,39(10):771-775