Identification of a novel LAMP2 mutation responsible for X-chromosomal dominant Danon disease.
Danon disease (DD) is a rare lysosomal glycogen storage disease with normal acid maltase activity, which is characterised clinically by cardiomyopathy and myopathy, and a variable degree of mental retardation. The causative gene, LAMP2, has been mapped to chromosome Xq24-q25. LAMP2 encodes a lysosome-associated membrane glycoprotein. We identified a novel LAMP2 mutation of the exon 8 splice acceptor site (IVS7-1G --> A) in an affected male and female, which predicts abnormal splicing. Both affected individuals presented solely with hypertrophic cardiomyopathy. Muscle weakness and mental impairment were absent. Diagnosis of Danon disease was established by muscle biopsy, when the male index patient developed transient severe muscle weakness following heart transplantation. Typical biopsy findings were also found in a heart muscle specimen. Demonstration of the LAMP2 mutation in affected male and female siblings is compatible with X-linked dominant inheritance. Danon disease should be actively looked for in cardiomyopathy patients.
Department of Pediatric Neurology and Muscle Disease, University Children's Hospital Freiburg, Mathildenstrasse 1, 79106 Freiburg, Germany.
J
J
Horváth
U-P
UP
Ketelsen
A
A
Geibel-Zehender
N
N
Boehm
H
H
Olbrich
R
R
Korinthenberg
H
H
Omran
D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D009202:Cardiomyopathies / Q000473:pathology / Q000601:surgery; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006003:Glycogen / Q000235:genetics* / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D009130:Muscle, Smooth / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*
D015703:Antigens, CD; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D006003:Glycogen