title: Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease.
abstract: Recent linkage analyses of nondiabetic African-American patients with focal segmental glomerulosclerosis (FSGS) have identified MYH9, encoding nonmuscle myosin heavy chain IIA (NMMHC-IIA), as a gene having a critical role in this disease. Abnormalities of the MYH9 locus also underlie rare autosomal dominant diseases such as May-Hegglin anomaly, and Sebastian, Epstein (EPS), and Fechtner (FTNS) syndromes that are characterized by macrothrombocytopenia and cytoplasmic inclusion bodies in granulocytes. Among these diseases, patients with EPS or FTNS develop progressive nephritis and hearing disability. We analyzed clinical features and pathophysiological findings of nine EPS-FTNS patients with MYH9 mutations at the R702 codon hot spot. Most developed proteinuria and/or hematuria in early infancy and had a rapid progression of renal impairment during adolescence. Renal histopathological findings in one patient showed changes compatible with FSGS. The intensity of immunostaining for NMMHC-IIA in podocytes was decreased in this patient compared with control patients. Thus, MYH9 R702 mutations display a strict genotype-phenotype correlation, and lead to the rapid deterioration of podocyte structure. Our results highlight the critical role of NMMHC-IIA in the development of FSGS.
authors.affiliation: Faculty of Medicine, Department of Pediatrics, The University of Tokyo, Tokyo, Japan. sekinet-tky@umin.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekine
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Konno
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Suzuko
authors.initials: S
authors.lastname: Moritani
authors.forename: Takuma
authors.initials: T
authors.lastname: Miura
authors.forename: Wai-shan
authors.initials: WS
authors.lastname: Wong
authors.forename: Hisanori
authors.initials: H
authors.lastname: Nishio
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nishiguchi
authors.forename: Miyako Yoshinari
authors.initials: MY
authors.lastname: Ohuchi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuyama
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Komei
authors.initials: K
authors.lastname: Ida
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Miura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Harita
authors.forename: Motoshi
authors.initials: M
authors.lastname: Hattori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Horita
authors.forename: Takashi
authors.initials: T
authors.lastname: Igarashi
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics*; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D009394:Nephritis, Hereditary / Q000235:genetics; D011507:Proteinuria / Q000209:etiology*; D013921:Thrombocytopenia / Q000235:genetics / Q000151:congenital; D055815:Young Adult
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains