title: Phenotypic heterogeneity in two unrelated Danon patients associated with the same LAMP-2 gene mutation.
abstract: Danon disease, an X-linked cardioskeletal myopathy caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2), is clinically characterized by cardiomyopathy, myopathy, and variable mental retardation. The pathological hallmark of the disease is the absence of LAMP-2 immunohistochemical staining in muscle. The LAMP-2 gene mutations reported thus far are generally private mutations. We describe two cases of Danon disease with different clinical presentation, in whom we identified the same exon skipping mutation c.928G>A in the LAMP-2 gene. The first patient was affected by an early onset myopathy and hypertrophic cardiomyopathy (HCM) that partially improved with drug treatment. A first muscle biopsy at age 4 months showed markedly increased glycogen, and acid maltase deficiency was ruled out biochemically. A second muscle biopsy, performed at age 3(1/2) years, showed very mild abnormalities. The second child at age 15 years had mild, diffuse muscle weakness and wasting, moderate mental deficiency, and HCM. Two serial biopsies performed at age 8 and 15 years showed similar findings of multiple esterase-positive vacuoles in type I myofibers. In both patients the immunohistochemical study demonstrated the absence of LAMP-2 in skeletal muscle.
authors.affiliation: Unit of Molecular Medicine, Division of Metabolism, Bambino Gesù Children's Hospital Rome and Palidoro, Italy. ebertini@tin.it.
authors.forename: E
authors.initials: E
authors.lastname: Bertini
authors.forename: M A
authors.initials: MA
authors.lastname: Donati
authors.forename: P
authors.initials: P
authors.lastname: Broda
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: S
authors.initials: S
authors.lastname: Petrini
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
authors.forename: L
authors.initials: L
authors.lastname: Ballerini
authors.forename: R
authors.initials: R
authors.lastname: Boldrini
authors.forename: A
authors.initials: A
authors.lastname: D'Amico
authors.forename: E
authors.initials: E
authors.lastname: Pasquini
authors.forename: C
authors.initials: C
authors.lastname: Minetti
authors.forename: F M
authors.initials: FM
authors.lastname: Santorelli
authors.forename: C
authors.initials: C
authors.lastname: Bruno
mesh_terms: D000293:Adolescent; D015152:Blotting, Northern / Q000379:methods; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D012333:RNA, Messenger