Patients with Epstein–Fechtner syndromes owing to MYH9 R702 mutations develop progressive proteinuric renal disease
| Autor: | Shinji Kunishima, Motoshi Hattori, Yutaka Harita, Hirokazu Kanegane, Shigeru Horita, Suzuko Moritani, Shigeru Tsuchiya, Hisanori Nishio, Miyako Yoshinari Ohuchi, Komei Ida, Takashi Sekine, Hidehiko Saito, Satoshi Sasaki, Takeshi Matsuyama, Mutsuko Konno, Toshihiro Nishiguchi, Kenichiro Miura, Wai Shan Wong, Takuma Miura, Takashi Igarashi |
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| Rok vydání: | 2010 |
| Předmět: |
Nephrology
Adult Male medicine.medical_specialty Pathology podocyte Adolescent Renal glomerulus Hearing Loss Sensorineural Nephritis Hereditary urologic and male genital diseases Article Nephropathy MYH9 Young Adult Focal segmental glomerulosclerosis Internal medicine medicine Humans Child Fechtner syndrome Myosin Heavy Chains business.industry urogenital system Molecular Motor Proteins medicine.disease Thrombocytopenia Proteinuria FSGS Epstein Syndrome Child Preschool Mutation Epstein syndrome Disease Progression Female Kidney Diseases business Nephritis NMMHC-IIA Kidney disease |
| Zdroj: | Kidney International. 78(2):207-214 |
| ISSN: | 0085-2538 |
| DOI: | 10.1038/ki.2010.21 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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