1例遗传性MYH9相关疾病家系老年白内障患者临床和基因突变特点

Clinical and molecular biological characteristics of a presenile cataract with MYH9-RD family

目的了解海南省MYH9相关疾病家系1例老年白内障患者的临床表现和MYH9基因突变特点。方法对该患者进行临床体征评估和实验室检测;应用光学和电子显微镜进行外周血细胞形态和超微结构分析;对MYH9基因的40个外显子和侧翼区进行PCR扩增和测序,确认突变类型。结果通过临床表现和实验室检测,该患者具有典型的巨大血小板、血小板减少和粒细胞内包涵体三联症,且表型复杂多样如伴有长期高脂血症、蛋白尿、肌酐升高、心功能不全、转氨酶升高、哮喘、鼻炎等多种疾病;MYH9基因40个外显子和侧翼区未见致病突变(除25号外显子发生一同义突变,突变类型为A1143A)。结论该老年白内障患者MYH9基因未见致病性突变,其具有的严重临床表型可能与存在新的基因突变类型或新的致病基因有关。

Objective To characterize the clinical phenotypes and identify the mutations of the non-muscle myosin heavy chain type Ⅱ-A （NMMHC-ⅡA） gene of the cataract with MYH9-related disease（MYH9-RD） in Hainan.Methods A screen was made for the presence or absence of abnormal hemostasis;Technique of light and electron microscope was applied to analyze the cell morphology and ultrastructure of peripheral blood;PCR was used to amplify all the 40 exons and franking regions of the MYH9 gene,and the amplified exon DNA was subjected to sequence analysis.Results The presenile cataract not only had thrombocytopenia,giant platelets and inclusion bodies in granulocytes,but also suffered from hyperlipemia,proteinuria,abnormal hepatic function,serum creatinine rising,asthma and disordered action of heart etc;No pathogenic mutation was detected in the exon and franking regions of MYH9 gene except a synonymous mutation（A1143A） in the exon 25.Conclusions The presenile cataract with serious clinical entities may be resulted from a novel mutation or another novel pathogenic gene with MYH9-RD.