Danon disease presenting with dilated cardiomyopathy and a complex phenotype

Matthew R.G. Taylor, Lisa Ku, Dobromir Slavov, Jean Cavanaugh, Mark Boucek, Xiao Zhu, Sharon Graw, Elisa Carniel, Carl Barnes, Dianna Quan, Ryan Prall, Mark A. Lovell, Gary Mierau, Patsy Ruegg, Naresh Mandava, Michael R. Bristow, Jeffrey Towbin, Luisa Mestroni

Research output: Contribution to journalArticle

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Abstract

X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families. Here we report long-term follow-up of the second family (XLCM-2), for which a DMD mutation was never found. Analysis of the lysosome-associated membrane protein-2 (LAMP-2) gene detected a novel mutation, confirming a diagnosis of Danon disease. The broad phenotype in this family included dilated and hypertrophic cardiomyopathy, cardiac pre-excitation, skeletal myopathy with high serum creatine kinase, cognitive impairment (in males), and a pigmentary retinopathy in affected females. Cardiac biopsy specimens showed extensive vacuolar changes in an affected adult male. Remarkably, the skeletal muscle biopsy in a 13-month-old mutation-carrying male showed no vacuolization by standard histology. We conclude that XLCM may be the presenting sign of Danon disease and, in the presence of a familial history of HCM, pre-excitation, skeletal muscle involvement and retinal pigmentary dystrophy should prompt LAMP-2 clinical testing. Furthermore, the absence of vacuolar myopathy in biopsies from young patients may not exclude Danon disease.

Original languageEnglish (US)
Pages (from-to)830-835
Number of pages6
JournalJournal of Human Genetics
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

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Glycogen Storage Disease Type IIb
Dilated Cardiomyopathy
Lysosome-Associated Membrane Glycoproteins
Phenotype
Mutation
Biopsy
Skeletal Muscle
Retinal Dystrophies
Dystrophin
Retinitis Pigmentosa
Hypertrophic Cardiomyopathy
Muscular Diseases
Creatine Kinase
Genes
Histology
Serum
Dmd-Associated Dilated Cardiomyopathy

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Taylor, M. R. G., Ku, L., Slavov, D., Cavanaugh, J., Boucek, M., Zhu, X., ... Mestroni, L. (2007). Danon disease presenting with dilated cardiomyopathy and a complex phenotype. Journal of Human Genetics, 52(10), 830-835. https://doi.org/10.1007/s10038-007-0184-8

Danon disease presenting with dilated cardiomyopathy and a complex phenotype. / Taylor, Matthew R.G.; Ku, Lisa; Slavov, Dobromir; Cavanaugh, Jean; Boucek, Mark; Zhu, Xiao; Graw, Sharon; Carniel, Elisa; Barnes, Carl; Quan, Dianna; Prall, Ryan; Lovell, Mark A.; Mierau, Gary; Ruegg, Patsy; Mandava, Naresh; Bristow, Michael R.; Towbin, Jeffrey; Mestroni, Luisa.

In: Journal of Human Genetics, Vol. 52, No. 10, 01.10.2007, p. 830-835.

Research output: Contribution to journalArticle

Taylor, MRG, Ku, L, Slavov, D, Cavanaugh, J, Boucek, M, Zhu, X, Graw, S, Carniel, E, Barnes, C, Quan, D, Prall, R, Lovell, MA, Mierau, G, Ruegg, P, Mandava, N, Bristow, MR, Towbin, J & Mestroni, L 2007, 'Danon disease presenting with dilated cardiomyopathy and a complex phenotype', Journal of Human Genetics, vol. 52, no. 10, pp. 830-835. https://doi.org/10.1007/s10038-007-0184-8
Taylor MRG, Ku L, Slavov D, Cavanaugh J, Boucek M, Zhu X et al. Danon disease presenting with dilated cardiomyopathy and a complex phenotype. Journal of Human Genetics. 2007 Oct 1;52(10):830-835. https://doi.org/10.1007/s10038-007-0184-8
Taylor, Matthew R.G. ; Ku, Lisa ; Slavov, Dobromir ; Cavanaugh, Jean ; Boucek, Mark ; Zhu, Xiao ; Graw, Sharon ; Carniel, Elisa ; Barnes, Carl ; Quan, Dianna ; Prall, Ryan ; Lovell, Mark A. ; Mierau, Gary ; Ruegg, Patsy ; Mandava, Naresh ; Bristow, Michael R. ; Towbin, Jeffrey ; Mestroni, Luisa. / Danon disease presenting with dilated cardiomyopathy and a complex phenotype. In: Journal of Human Genetics. 2007 ; Vol. 52, No. 10. pp. 830-835.
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