Document Detail

Patients with Epstein-Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease.
MedLine Citation:
PMID:  20200500     Owner:  NLM     Status:  MEDLINE    
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.
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-03
Journal Detail:
Title:  Kidney international     Volume:  78     ISSN:  1523-1755     ISO Abbreviation:  Kidney Int.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-30     Completed Date:  2010-12-02     Revised Date:  2011-01-26    
Medline Journal Info:
Nlm Unique ID:  0323470     Medline TA:  Kidney Int     Country:  United States    
Other Details:
Languages:  eng     Pagination:  207-14     Citation Subset:  IM    
Faculty of Medicine, Department of Pediatrics, The University of Tokyo, Tokyo, Japan.
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MeSH Terms
Child, Preschool
Disease Progression
Hearing Loss, Sensorineural / genetics
Kidney Diseases / etiology*
Molecular Motor Proteins / genetics*
Myosin Heavy Chains / genetics*
Nephritis, Hereditary / genetics
Proteinuria / etiology*
Thrombocytopenia / genetics
Young Adult
Reg. No./Substance:
0/MYH9 protein, human; 0/Molecular Motor Proteins; 0/Myosin Heavy Chains
Comment In:
Kidney Int. 2010 Jul;78(2):130-3   [PMID:  20588287 ]

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