title: Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children.
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.
  
  
  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.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Yang
authors.forename: Colin J
authors.initials: CJ
authors.lastname: McMahon
authors.forename: Liana R
authors.initials: LR
authors.lastname: Smith
authors.forename: Jeathrina
authors.initials: J
authors.lastname: Bersola
authors.forename: Adekunle M
authors.initials: AM
authors.lastname: Adesina
authors.forename: John P
authors.initials: JP
authors.lastname: Breinholt
authors.forename: Debra L
authors.initials: DL
authors.lastname: Kearney
authors.forename: William J
authors.initials: WJ
authors.lastname: Dreyer
authors.forename: Susan W
authors.initials: SW
authors.lastname: Denfield
authors.forename: Jack F
authors.initials: JF
authors.lastname: Price
authors.forename: Michelle
authors.initials: M
authors.lastname: Grenier
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Kertesz
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Clunie
authors.forename: Susan D
authors.initials: SD
authors.lastname: Fernbach
authors.forename: James F
authors.initials: JF
authors.lastname: Southern
authors.forename: Stuart
authors.initials: S
authors.lastname: Berger
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: Karla R
authors.initials: KR
authors.lastname: Bowles
authors.forename: Neil E
authors.initials: NE
authors.lastname: Bowles
mesh_terms: D000293:Adolescent; D002312:Cardiomyopathy, Hypertrophic / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D015331:Cohort Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D005787:Gene Frequency; D052120:Glycogen Storage Disease Type IIb / Q000150:complications* / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000209:etiology; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000473:pathology; D014927:Wolff-Parkinson-White Syndrome / Q000209:etiology
chemical_list: D018389:Codon, Nonsense; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins