Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children

Zhao Yang, Colin J. McMahon, Liana R. Smith, Jeathrina Bersola, Adekunle M. Adesina, John P. Breinholt, Debra L. Kearney, William J. Dreyer, Susan W. Denfield, Jack F. Price, Michelle Grenier, Naomi J. Kertesz, Sarah K. Clunie, Susan D. Fernbach, James F. Southern, Stuart Berger, Jeffrey Towbin, Karla R. Bowles, Neil E. Bowles

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Abstract

Background - Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. Methods and Results - LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. Conclusions - LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.

Original languageEnglish (US)
Pages (from-to)1612-1617
Number of pages6
JournalCirculation
Volume112
Issue number11
DOIs
StatePublished - Sep 13 2005

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Glycogen Storage Disease Type IIb
Hypertrophic Cardiomyopathy
Muscular Diseases
Dilated Cardiomyopathy
Mutation
Lysosome-Associated Membrane Glycoproteins
Pediatrics
Wolff-Parkinson-White Syndrome
Nonsense Codon
Left Ventricular Hypertrophy
Mutation Rate
Lysosomes
Cardiology
DNA Sequence Analysis
Siblings
Myocardium
Skeletal Muscle
Heart Failure
Mothers
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Yang, Z., McMahon, C. J., Smith, L. R., Bersola, J., Adesina, A. M., Breinholt, J. P., ... Bowles, N. E. (2005). Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation, 112(11), 1612-1617. https://doi.org/10.1161/CIRCULATIONAHA.105.546481

Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. / Yang, Zhao; McMahon, Colin J.; Smith, Liana R.; Bersola, Jeathrina; Adesina, Adekunle M.; Breinholt, John P.; Kearney, Debra L.; Dreyer, William J.; Denfield, Susan W.; Price, Jack F.; Grenier, Michelle; Kertesz, Naomi J.; Clunie, Sarah K.; Fernbach, Susan D.; Southern, James F.; Berger, Stuart; Towbin, Jeffrey; Bowles, Karla R.; Bowles, Neil E.

In: Circulation, Vol. 112, No. 11, 13.09.2005, p. 1612-1617.

Research output: Contribution to journalArticle

Yang, Z, McMahon, CJ, Smith, LR, Bersola, J, Adesina, AM, Breinholt, JP, Kearney, DL, Dreyer, WJ, Denfield, SW, Price, JF, Grenier, M, Kertesz, NJ, Clunie, SK, Fernbach, SD, Southern, JF, Berger, S, Towbin, J, Bowles, KR & Bowles, NE 2005, 'Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children', Circulation, vol. 112, no. 11, pp. 1612-1617. https://doi.org/10.1161/CIRCULATIONAHA.105.546481
Yang Z, McMahon CJ, Smith LR, Bersola J, Adesina AM, Breinholt JP et al. Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation. 2005 Sep 13;112(11):1612-1617. https://doi.org/10.1161/CIRCULATIONAHA.105.546481
Yang, Zhao ; McMahon, Colin J. ; Smith, Liana R. ; Bersola, Jeathrina ; Adesina, Adekunle M. ; Breinholt, John P. ; Kearney, Debra L. ; Dreyer, William J. ; Denfield, Susan W. ; Price, Jack F. ; Grenier, Michelle ; Kertesz, Naomi J. ; Clunie, Sarah K. ; Fernbach, Susan D. ; Southern, James F. ; Berger, Stuart ; Towbin, Jeffrey ; Bowles, Karla R. ; Bowles, Neil E. / Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. In: Circulation. 2005 ; Vol. 112, No. 11. pp. 1612-1617.
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abstract = "Background - Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. Methods and Results - LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4{\%}), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. Conclusions - LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.",
author = "Zhao Yang and McMahon, {Colin J.} and Smith, {Liana R.} and Jeathrina Bersola and Adesina, {Adekunle M.} and Breinholt, {John P.} and Kearney, {Debra L.} and Dreyer, {William J.} and Denfield, {Susan W.} and Price, {Jack F.} and Michelle Grenier and Kertesz, {Naomi J.} and Clunie, {Sarah K.} and Fernbach, {Susan D.} and Southern, {James F.} and Stuart Berger and Jeffrey Towbin and Bowles, {Karla R.} and Bowles, {Neil E.}",
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T1 - Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children

AU - Yang, Zhao

AU - McMahon, Colin J.

AU - Smith, Liana R.

AU - Bersola, Jeathrina

AU - Adesina, Adekunle M.

AU - Breinholt, John P.

AU - Kearney, Debra L.

AU - Dreyer, William J.

AU - Denfield, Susan W.

AU - Price, Jack F.

AU - Grenier, Michelle

AU - Kertesz, Naomi J.

AU - Clunie, Sarah K.

AU - Fernbach, Susan D.

AU - Southern, James F.

AU - Berger, Stuart

AU - Towbin, Jeffrey

AU - Bowles, Karla R.

AU - Bowles, Neil E.

PY - 2005/9/13

Y1 - 2005/9/13

N2 - Background - Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. Methods and Results - LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. Conclusions - LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.

AB - Background - Some patients with hypertrophic cardiomyopathy (HCM) or left ventricular hypertrophy also present with skeletal myopathy and Wolff-Parkinson-White (WPW) syndrome; mutations in the gene encoding the lysosome-associated protein-2 (LAMP-2) have been identified in these patients, suggesting that some of these patients have Danon disease. In this study we investigated the frequency of LAMP2 mutations in an unselected pediatric HCM population. Methods and Results - LAMP2 was amplified from genomic DNA isolated from peripheral lymphocytes of 50 patients diagnosed with HCM and analyzed by direct DNA sequencing. In 2 of the 50 probands (4%), nonsense mutations were identified. In 1 family the proband initially presented with HCM as a teenager, which progressed to dilated cardiomyopathy (DCM) and heart failure. Skeletal myopathy and WPW were also noted. The teenage sister of the proband is a carrier of the same LAMP2 mutation and has HCM without skeletal myopathy or WPW. The other proband presented with HCM, WPW, and skeletal myopathy as a teenager, whereas his carrier mother developed DCM during her 40s. Skeletal and cardiac muscle sections revealed the absence of LAMP-2 on immunohistochemical staining. Conclusions - LAMP2 mutations may account for a significant proportion of cases of HCM in children, especially when skeletal myopathy and/or WPW is present, suggesting that Danon disease is an underrecognized entity in the pediatric cardiology community.

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EP - 1617

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SN - 0009-7322

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