Clinicopathological features and autophagic pathway of autophagic vacuolar myopathy and

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461323
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nara Medical University
• Principal Investigator: Sugie Kazuma 奈良県立医科大学, 医学部, 准教授 (60347549)
• Co-Investigator(Kenkyū-buntansha): NISHINO ICHIZO 国立精神・神経医療研究センター, 神経研究所疾病研究第一部, 部長 (00332388) ; UENO SATOSHI 奈良県立医科大学, 神経内科, 教授 (40184949)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 自己貪食空胞性ミオパチー / 自己貪食空胞 / オートファジー / Danon病 / LAMP-2 / ライソゾーム

Outline of Final Research Achievements

Danon disease, an X-linked dominant vacuolar cardiomyopathy and skeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). The clinical features and the prevalences of Danon disease have not been well established. On a nationwide survey, we identified 28 Danon disease patients (16 men and 12 women). Hypertrophic cardiomyopathy (HCM) was documented in most men, while dilated cardiomyopathy was more common among women. Pathologically, we found autophagic vacuoles with sarcolemmal features (AVSF) and LAMP-2 deficiency in muscle fibers. AVSF expressed virtually all sarcolemmal proteins on their vacuolar membranes. In addition, variable proteins associated with autophagic pathway were expressed in AVSF. In conclusion, Danon disease is a very rare muscular disorder and may be primarily caused by lysosomal dysfunctions. Cardiomyopathy is the most important prognostic factor and the main cause of death among Danon disease patients.

Free Research Field

神経内科