Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease

Takashi Sekine, Mutsuko Konno, Satoshi Sasaki, Suzuko Moritani, Takuma Miura, Wai Shan Wong, Hisanori Nishio, Toshihiro Nishiguchi, Miyako Yoshinari Ohuchi, Shigeru Tsuchiya, Takeshi Matsuyama, Hirokazu Kanegane, Komei Ida, Kenichiro Miura, Yutaka Harita, Motoshi Hattori, Shigeru Horita, Takashi Igarashi, Hidehiko Saito, Shinji Kunishima

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85 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)207-214
Number of pages8
JournalKidney International
Issue number2
Publication statusPublished - Jul 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Nephrology


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