Objective: To investigate the clinical phenotype and gene mutation characteristics of MYH9-related disorder (MYH9-RD). Methods: The clinical data of 66 patients with MYH9-RD in the First Affiliated Hospital of Soochow University from January 2010 to December 2022 were retrospectively analyzed. According to the bleeding symptom, the patients were divided into bleeding and non-bleeding group, and according to the mutation sites, the patients were divided into non-muscle myosin heavy chain ⅡA head region (MD) and tail region (TD) mutation group. Statistical analysis was made to explore the clinical features in different groups such as platelet counts, bleeding, renal function, cataracts and hearing as well as MYH9 gene mutations. Results: A total of 66 MYH9-RD patients were included, with 28 males and 38 females, diagnosis age of 1-63(26±2) years. And 41% (27/66) of the patients had no family history. All patients presented with macrothrombocytopenia and normal platelet aggregation(10/10), 92% (54/59) of the patients had visible blue inclusion bodies in neutrophils, 30% (20/66) had bleeding symptoms, 45% (22/49) had proteinuria or glomerulonephropathy, 20% (8/41) had bilateral hearing impairment, and 10% (4/42) had bilateral cataracts. 18 mutation sites were identified in total, including 15 missense, 1 splicing and 2 termination mutations. Among them, p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys mutations were identified in 56% (29/52) of the patients, and p.Ser96Leu, Arg1165Cys and p.Glu1841Lys mutations were recurrent mutations, while p.Ala44Thr, p.Asp1447Ala and c.3838-2A>G mutations were novel mutations. The average platelet count of patients in bleeding group was (19±3)×109/L, which was significantly less than (36±3)×109/L in non-bleeding group (P<0.001). Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts (all P<0.05). Conclusion: Mutations of p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys in MYH9 gene are hotspot mutations for MYH9-RD patients, Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts.
目的： 分析MYH9相关疾病的临床表型及基因突变特征。 方法： 回顾性分析2010年1月至2022年12月苏州大学附属第一医院66例MYH9相关疾病患者临床资料。根据有无出血将患者分为出血组和未出血组，根据突变位点将患者分为非肌性肌球蛋白重链ⅡA头部区域（MD）突变组和尾部区域（TD）突变组。统计分析不同组别患者血小板数量、出血情况、肾功能、白内障及听力等基本临床表型特征以及MYH9基因突变情况。 结果： 66例MYH9相关疾病患者中，其中男28例，女38例，确诊年龄为1~63（26±2）岁，41%（27/66）为散发病例。所有患者均出现血小板减少伴有巨大血小板，血小板聚集功能（10/10）均正常。92%（54/59）患者中性粒细胞内可见蓝色的包涵体，30%（20/66）患者存在出血，45%（22/49）患者存在蛋白尿或肾小球肾病，20%（8/41）患者存在双侧听力受损，10%（4/42）患者存在双侧白内障。共发现18个基因突变位点，包括错义突变15个、剪切突变1个、终止突变2个，其中56%（29/52）患者存在p.Asp1424Asn、p.Arg1933*及p.Arg702His/Cys突变，p.Ser96Leu、Arg1165Cys及p.Glu1841Lys突变为重现型突变，p.Ala44Thr、p.Asp1447Ala及c.3838-2A>G突变为新发突变。出血组患者血小板数量为（19±3）×109/L，明显少于未出血组的（36±3）×109/L（P<0.001）。与TD突变组比较，MD突变组血小板数量更少，出血等级更高，肾脏受累程度、听力受损及白内障等临床表型症状更重（均P<0.05）。 结论： p.Asp1424Asn、p.Arg1933*及p.Arg702His/Cys为MYH9相关疾病患者的热点突变。MD突变组血小板数量更少，出血等级更高，肾脏受累程度、听力受损及白内障等临床表型症状重于TD突变组。.