title: Identification of Two Novel LAMP2 Gene Mutations in Danon Disease.
abstract: Danon disease is a rare X-linked inherited disorder characterized by massive left ventricular hypertrophy, skeletal muscle dystrophy, and mental retardation. The disease is caused by mutations in the LAMP2 gene encoding for lysosome-associated membrane protein-2.
  
  
  
  Two young male patients with hypertrophic cardiomyopathy, characterized by marked, concentric left ventricular hypertrophy, elevated levels of creatine kinase, and manifest limb-girdle muscular dystrophy in 1 case, were investigated. Genetic screening included direct sequencing of the whole coding sequence of the LAMP2 gene.
  
  
  
  Genetic analysis identified 2 novel LAMP2 gene mutations. In Family A, a G-A transition (c.962G > A) leading to a nonsense mutation at codon 321 (p.Trp321Ter), and in Family B, a one-nucleotide insertion (c.973insC) leading to a full frame-shift (p.Pro324+24X) was detected in exon 8 of the LAMP2 gene. Family screening identified 8 mutation carriers, with 4 nonpenetrant cases and 3 additional, probably affected family members without DNA diagnosis. The cardiac phenotype was hypertrophic cardiomyopathy in all cases, including female mutation carriers. Five disease-related deaths occurred in the families, at an average age of 33 ± 16 years, which was clearly lower in male than in female patients (28 ± 7 vs 42 ± 25 years). A high prevalence of arrhythmias or conduction abnormalities was also observed.
  
  
  
  The reported 2 novel LAMP2 gene mutation carrier families, one of them being one of the largest reported to date, highlight the malignant clinical course of Danon disease, characterized by a high rate of disease-related death at an early age and a high prevalence of arrhythmias or conduction abnormalities.
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Csányi
authors.affiliation: Department of Paediatrics, University of Medicine and Pharmacy "Victor Babes", Timisoara, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Popoiu
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Lidia
authors.initials: L
authors.lastname: Hategan
authors.affiliation: Institute of Biophysics, Bioinformatics Group, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Hegedűs
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Nagy
authors.affiliation: Department of Pediatrics, University of Szeged, Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Rácz
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Márta
authors.initials: M
authors.lastname: Hőgye
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Sághy
authors.affiliation: Department of Pathology, University of Szeged, Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Iványi
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Csanády
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Forster
authors.affiliation: 2nd Department of Internal Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary. Electronic address: sepp.robert@med.u-szeged.hu.
authors.forename: Róbert
authors.initials: R
authors.lastname: Sepp
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics; D018389:Codon, Nonsense; D005260:Female; D016368:Frameshift Mutation; D006580:Genetic Carrier Screening; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics*; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics*; D008297:Male; D010375:Pedigree; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2