Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation 2005 Sep 13;112(11):1612-7
Date
09/08/2005Pubmed ID
16144992DOI
10.1161/CIRCULATIONAHA.105.546481Scopus ID
2-s2.0-24944575163 (requires institutional sign-in at Scopus site) 157 CitationsAbstract
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 List
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 JA, Bowles KR, Bowles NEMESH terms used to index this publication - Major topics in bold
AdolescentCardiomyopathy, Hypertrophic
Child
Child, Preschool
Codon, Nonsense
Cohort Studies
Female
Fluorescent Antibody Technique
Gene Frequency
Glycogen Storage Disease Type IIb
Humans
Infant
Infant, Newborn
Lysosomal-Associated Membrane Protein 2
Male
Muscle, Skeletal
Muscular Diseases
Myocardium
Papillary Muscles
Wolff-Parkinson-White Syndrome
