title: Danon disease caused by two novel mutations of the LAMP2 gene: implications for two ends of the clinical spectrum.
abstract: Danon disease is caused by mutations of the lysosome-associated membrane protein-2 (LAMP2) gene at Xq24. Male patients usually manifested as severe cardiomyopathy, mild myopathy and mental retardation. We describe two patients: the first patient presented with severe hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, proximal muscle weakness, and chronic painless diarrhea; the second patient manifested as limb-girdle muscle weakness, mild left ventricular diastolic dysfunction, sub-clinical neuropathy. Muscle biopsies indicated autophagic vacuolar myopathy. Immunologic analysis demonstrated absence of the LAMP2 protein in the first patient, while a smear of expression was detected in the second patient. Two nonsense mutations (p.E298X and p. K402X) were identified in the two cases, respectively located in exon 7 and exon 9B of the LAMP2 gene. Our findings indicated that patients with Danon disease caused by mutations in exon 1 – 8 manifested as a typically severe phenotype, while patients with mutations in exon 9 of the LAMP2B isoform presented with a relatively benign phenotype.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing, China.
authors.forename: Daojun
authors.initials: D
authors.lastname: Hong
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Shi
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000293:Adolescent; D001706:Biopsy; D018389:Codon, Nonsense; D005091:Exons; D052120:Glycogen Storage Disease Type IIb / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000235:genetics*; D008297:Male; D010641:Phenotype; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins