Danon disease: case report and detection of new mutation.
Danon disease is an X-linked disorder resulting from mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. We report a male patient with skeletal myopathy, mental retardation, and massive hypertrophic obstructive cardiomyopathy necessitating heart transplantation. Immunohistochemistry of skeletal muscle and leukocytes, western blot analysis of leukocytes and cardiac muscle, flow cytometry, and DNA sequencing were performed. Muscle biopsy revealed autophagic vacuolar myopathy and lack of immunohistochemically detectable LAMP-2. Diagnosis of Danon disease was confirmed by western blot analysis of myocardial tissue and peripheral blood sample of the patient showing deficiency of LAMP-2 in myocardium and leukocytes. Moreover, absence of LAMP-2 in lymphocytes, monocytes and granulocytes was shown by flow cytometric analysis. Genetic analysis of the LAMP2 gene revealed a novel 1-bp deletion at position 179 (c.179delC) at the 3' end of exon 2, resulting in a frameshift with a premature stop codon.
Regelsberger
G
G
Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, POB 48, 1097, Vienna, Austria. guenther.regelsberger@meduniwien.ac.at
Höftberger
R
R
Pickl
W F
WF
Zlabinger
G J
GJ
Körmöczi
U
U
Salzer-Muhar
U
U
Luckner
D
D
Bodamer
O A
OA
Mayr
J A
JA
Muss
W H
WH
Budka
H
H
Bernheimer
H
H
D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
D018389:Codon, Nonsense; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins