title: Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease).
abstract: A family with several cases of severe cardiomyopathy and moderate myopathy is described, affecting two brothers and their cousin as well as their mothers. One boy died of sudden cardiac arrest at 17 years of age. The two brothers were treated with an implantable defibrillator and their mother died suddenly at 40 years of age. Muscle biopsy in males showed vacuolar myopathy in two cases, and no abnormality on standard staining in the third case. Cardiac biopsies showed hypertrophic and vacuolated fibres. Complete absence of LAMP-2 was demonstrated by immunohistochemistry on the vacuolated skeletal and cardiac muscle, but also on the morphologically normal skeletal muscle. Sequencing of LAMP-2 gene showed a novel S157X mutation in exon 4. Danon disease is a rare and potentially lethal cause of hypertrophic cardiomyopathy. Diagnosis can be made by immunohistochemistry performed on cardiac or muscle biopsy, and confirmed by genetic analysis, which also allows for easy family screening and counselling.
authors.affiliation: Institut de Pathologie, Division de Neuropathologie, Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland.
authors.forename: J A
authors.initials: JA
authors.lastname: Lobrinus
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: M
authors.initials: M
authors.lastname: Payot
authors.forename: X
authors.initials: X
authors.lastname: Jeanrenaud
authors.forename: A
authors.initials: A
authors.lastname: Bottani
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
authors.forename: J
authors.initials: J
authors.lastname: Schlaepfer
authors.forename: M
authors.initials: M
authors.lastname: Fromer
authors.forename: P-Y
authors.initials: PY
authors.lastname: Jeannet
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D001706:Biopsy / Q000379:methods; D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D012694:Serine / Q000235:genetics; D013194:Staining and Labeling / Q000379:methods
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D012694:Serine