非家族性May—Hegglin异常伴MYH9基因R1933X突变及I1626V多态性

A non-familial May-Hegglin anomaly accompanying with MYH9 gene R1933X mutation and I1626V polymorphism

目的鉴定1例May—Hegglin异常（MHA）先证者非肌性肌球蛋白重链9基因（MYH9）突变类型，并对其无临床及血液学表型的家系成员进行基因分析，以确定先证者MYH9基因突变与其父母该基因遗传的非相关性。方法用透射电镜观察先证者外周血粒细胞包涵体，用扫描电镜观察患者外周血巨大血小板形态；用PCR技术扩增患者及其父母MYH9基因突变热点区域，并对PCR产物进行正反向测序，确定其突变位点。结果①先证者具有典型的“血小板减少、巨大血小板、中性粒细胞包涵体”三联征，MHA诊断成立；而患者父母及兄长均健康。②透射及扫描电镜观察证实先证者外周血存在巨大血小板及粒细胞包涵体。③先证者MYH9基因40号外显子第5797位核苷酸存在C→T突变，该突变导致编码的非肌性肌球蛋白重链ⅡA（NMMHC—A）蛋白第1933位精氨酸转变为终止密码子（R1933X）；先证者MYH9基因33号外显子存在4876A→G杂合突变；先证者父母均未检测出R1933X突变，其母不存在4876A→G多态性，其父为4876A→G多态性的纯合子。结论本例MHA患者缺乏常染色体显性遗传家族史，为“散发”病例；该患者MYH9基因40号外显子5797C→T突变为致病突变，而33号外显子4876A→G突变为一多态性。

Objectives To identify the nonmuscle myosin heavy chain 9 （ MYH9 ） gene mutation site in a May-Hegglin anomaly（MHA） patient, and to analyze the genotype of her relatives to exclude the inherit correlation between the proband and her family members. Methods Inclusion bodies in neutrophils of the proband were examined by transmission electron microscope, and giant platelets by scanning electron microscope. The mutation ＂hot spot＂ on the MYH9 gene of the proband and her family members was amplified with polymerase chain reaction（ PCR）, and then sequenced in both directions to identify the mutant site. Results ①The proband manifested with the typical MHA triad of giant platelet, thrombocytopenia and Dohle-like inclusion bodies in neutrophil. However, all of the proband＇ s family members had no such anomaly. ② Transmission electron microscope and scanning electron microscope confirmed that giant platelets and neutrophils inclusion bodies existed in the proband peripheral blood cells. ③There was a missense mutation 5797 C →T in the exon 40 of MYH9 gene which led to Arg changing into termination codon （Arg1933stop）. The proband also had a heterozygous mutation 4876A→G in exon 33. There was no abnormal finding in the sites mentioned above in her mother, while her father carried the homozygous 4876A→G mutation. Conclusions This MHA case is a sporadic one, in whose family a mode for autosomal dominant inheritance can not be established. The 5797C→T substitution in MYH9 gene is a pathogenic mutation, however, 4876A→G is simply a polymorphism.