[Analysis of clinical phenotype and gene mutation characteristics of MYH9-related disorder]

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.