一常染色体显性May-Hegglin异常家系致病基因的突变分析  

Analysis of gene mutation in a family featuring autosomal dominant May-Hegglin anomaly

作　　者：冯亚佩[1] 郭小凡[1] 李琳[2] 李江夏[1] 刘中路[2] 朱晓燕[2] 刘奇迹[1] 

机构地区：[1]山东大学医学院医学遗传研究所,济南250012 [2]临沂市人民医院

出　　处：《中华医学遗传学杂志》2013年第3期305-308,共4页Chinese Journal of Medical Genetics

基　　金：基金项目：国家自然科学基金（81072452,81273281）

摘　　要：目的分析1个May-Hegglin异常（May-Hegglinanomaly，MHA）家系的表型特点及非肌性肌球蛋白重链9基因（MyH9）突变的类型。方法对先证者及其家系成员进行详细的临床检查和血细胞镜检等实验室检查。采集家系成员的外周血，提取基因组DNA。用PCR技术扩增先证者MyH9基因第10、25、26、30、38、40外显子，测序并分析PCR产物的核苷酸序列。确定突变位点后，利用1对错配引物分别扩增家系中的其余患者及正常成员的对应基因区域，之后进行PCR扩增片段的TaqI限制性内切酶琼脂糖凝胶电泳图谱分析，以资对照和鉴定。结果本家系中MHA患者具有典型的“血小板减少、巨大血小板、粒细胞包涵体”三联征。所有患者在MYH9基因的第38外显子第5521位核苷酸均存在杂合错义突变C．5521G〉A（P．Glul841Lys），且该突变与疾病表型共分离。结论该MHA家系的致病基因为MYH9。C．5521G〉A突变为中国人群的一个突变热点。Objective To analyze clinical features and mutation in MYH9 gene for a family featuring autosomal dominant May-Hegglin anomaly. Methods Clinical and pathological features of all family members were analyzed. Blood samples were collected from the proband and other family members, and genomic DNA was extracted. Potential mutations of MYH9 gene exons 10, 25, 26, 30, 38 and 40 were screened with PCR and direct sequencing. After a mutation was identified in the proband, other affected members as well as healthy members from this family were analyzed with a pair of primers to amplify the mutant site. The PCR products were digested with Taq I enzyme and analyzed with agarose gel eleetrophoresis. Results All affected members had bleeding tendency and typical features including giant platelets, thrombocytopenia and characteristic D6hle body-like leukocyte inclusions. A heterozygous missense mutation c. 5521G〉A （p. Glu1841Lys） in exon 38 of the MYH9 gene was identified in all affected members from this family. Conclusion The variant, c. 5521G〉A （p. Glu1841Lys） of MYH9, has co- segregated with the phenotype in the family. The mutant site is a hot spot in Chinese population.

关 键 词：MAY-HEGGLIN异常 基因突变 非肌性肌球蛋白重链 MYH9基因 

分 类 号：R55[医药卫生—血液循环系统疾病]