title: Clinical, pathological, and genetic analysis of ten patients with MYH9-related disease.
abstract: MYH9-related disease (MYH9-RD) is an autosomal dominant disorder caused by mutations in the MYH9 gene. It is characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like granulocyte inclusions. In this study we report 10 unrelated patients with MYH9-RD in whom the following seven MYH9 gene mutations were found: W33R, p.Q1443_K1445dup, R702H, D1424N, E1841K, R1933X, and E1945X (the first two were novel mutations). The region of the MYH9 mutation determines in some regards the phenotype, but clinical expression can vary between individuals with the same mutation. The neutrophil inclusion bodies of two patients were too small to be detected, but could be found with immunofluorescence staining. Immunoblotting analysis revealed that the calculated NMMHC-IIA/β-actin ratio for MYH9-RD neutrophils was 39% of normal controls. Kidney biopsy showed segmental glomerulosclerosis and NMMHC-IIA expression was decreased in podocytes. This disease is not as rare as originally thought. In any individual with persistent macrothrombocytopenia and no response to corticosteroids and immunosuppressive agents, even if neutrophil inclusions were inconspicuous in routine staining, MYH9-RD should be suspected.
authors.affiliation: Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Key Lab of Thrombosis and Hemostasis of the Ministry of Health, Suzhou, China.
authors.forename: Xiong-hua
authors.initials: XH
authors.lastname: Sun
authors.forename: Zhao-yue
authors.initials: ZY
authors.lastname: Wang
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Yang
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Cao
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Zi-qiang
authors.initials: ZQ
authors.lastname: Yu
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.forename: Chang-geng
authors.initials: CG
authors.lastname: Ruan
mesh_terms: D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000648:ultrastructure; D002544:Cerebral Infarction / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020409:Molecular Motor Proteins / Q000235:genetics*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology / Q000151:congenital
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains