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A Nationwide Survey on Danon Disease in Japan

Danon disease, an X-linked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A tota...

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Autores principales: Sugie, Kazuma, Komaki, Hirofumi, Eura, Nobuyuki, Shiota, Tomo, Onoue, Kenji, Tsukaguchi, Hiroyasu, Minami, Narihiro, Ogawa, Megumu, Kiriyama, Takao, Kataoka, Hiroshi, Saito, Yoshihiko, Nonaka, Ikuya, Nishino, Ichizo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274850/
https://www.ncbi.nlm.nih.gov/pubmed/30413001
http://dx.doi.org/10.3390/ijms19113507
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author Sugie, Kazuma
Komaki, Hirofumi
Eura, Nobuyuki
Shiota, Tomo
Onoue, Kenji
Tsukaguchi, Hiroyasu
Minami, Narihiro
Ogawa, Megumu
Kiriyama, Takao
Kataoka, Hiroshi
Saito, Yoshihiko
Nonaka, Ikuya
Nishino, Ichizo
author_facet Sugie, Kazuma
Komaki, Hirofumi
Eura, Nobuyuki
Shiota, Tomo
Onoue, Kenji
Tsukaguchi, Hiroyasu
Minami, Narihiro
Ogawa, Megumu
Kiriyama, Takao
Kataoka, Hiroshi
Saito, Yoshihiko
Nonaka, Ikuya
Nishino, Ichizo
author_sort Sugie, Kazuma
collection PubMed
description Danon disease, an X-linked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A total of 39 patients (17 males, 22 females) from 20 families were identified in the analysis. All patients had cardiomyopathy. Of the 21 patients who died, 20 (95%) died of cardiac failure or sudden cardiac arrest. Most patients had hypertrophic cardiomyopathy. Wolf–Parkinson–White syndrome was present at a comparatively high incidence (54% in males, 22% in females). Only one female patient received a heart transplant, which is the most effective therapy. Histopathologically, all male patients showed autophagic vacuoles with sarcolemmal features in muscle. Half of the probands showed de novo mutations. Male patients showed completely absent LAMP-2 expression in muscle. In contrast, female patients showed decreased LAMP-2 expression, which is suggested to reflect LAMP-2 haploinsufficiency due to a heterozygous null mutation. In conclusion, Danon disease is an extremely rare muscular disorder in Japan. Cardiomyopathy is the most significant prognostic factor and the main cause of death. Our findings suggest that the present survey can extend our understanding of the clinical features of this rare disease.
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spelling pubmed-62748502018-12-15 A Nationwide Survey on Danon Disease in Japan Sugie, Kazuma Komaki, Hirofumi Eura, Nobuyuki Shiota, Tomo Onoue, Kenji Tsukaguchi, Hiroyasu Minami, Narihiro Ogawa, Megumu Kiriyama, Takao Kataoka, Hiroshi Saito, Yoshihiko Nonaka, Ikuya Nishino, Ichizo Int J Mol Sci Article Danon disease, an X-linked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). To clarify the clinicopathological features and management, we performed the first nationwide, questionnaire-based survey on Danon disease in Japan. A total of 39 patients (17 males, 22 females) from 20 families were identified in the analysis. All patients had cardiomyopathy. Of the 21 patients who died, 20 (95%) died of cardiac failure or sudden cardiac arrest. Most patients had hypertrophic cardiomyopathy. Wolf–Parkinson–White syndrome was present at a comparatively high incidence (54% in males, 22% in females). Only one female patient received a heart transplant, which is the most effective therapy. Histopathologically, all male patients showed autophagic vacuoles with sarcolemmal features in muscle. Half of the probands showed de novo mutations. Male patients showed completely absent LAMP-2 expression in muscle. In contrast, female patients showed decreased LAMP-2 expression, which is suggested to reflect LAMP-2 haploinsufficiency due to a heterozygous null mutation. In conclusion, Danon disease is an extremely rare muscular disorder in Japan. Cardiomyopathy is the most significant prognostic factor and the main cause of death. Our findings suggest that the present survey can extend our understanding of the clinical features of this rare disease. MDPI 2018-11-08 /pmc/articles/PMC6274850/ /pubmed/30413001 http://dx.doi.org/10.3390/ijms19113507 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sugie, Kazuma
Komaki, Hirofumi
Eura, Nobuyuki
Shiota, Tomo
Onoue, Kenji
Tsukaguchi, Hiroyasu
Minami, Narihiro
Ogawa, Megumu
Kiriyama, Takao
Kataoka, Hiroshi
Saito, Yoshihiko
Nonaka, Ikuya
Nishino, Ichizo
A Nationwide Survey on Danon Disease in Japan
title A Nationwide Survey on Danon Disease in Japan
title_full A Nationwide Survey on Danon Disease in Japan
title_fullStr A Nationwide Survey on Danon Disease in Japan
title_full_unstemmed A Nationwide Survey on Danon Disease in Japan
title_short A Nationwide Survey on Danon Disease in Japan
title_sort nationwide survey on danon disease in japan
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274850/
https://www.ncbi.nlm.nih.gov/pubmed/30413001
http://dx.doi.org/10.3390/ijms19113507
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