title: Novel LAMP2 mutations in Chinese patients with Danon disease cause varying degrees of clinical severity.
abstract: OBJECTIVE
  Danon disease is an Xlinked dominant lysosomal glycogen storage disorder characterized by cardiomyopathy, skeletal myopathy, and mental retardation. This study described two Chinese cases of Danon disease in order to broaden the phenotypic and genetic spectrum.
  
  
  METHODS
  Clinical data were collected and LAMP2 mutations were analyzed.
  
  
  RESULTS
  Patient A had fluctuating limb weakness during 6 months follow-up and was diagnosed with drug-induced myopathy due to anti-hepatitis B therapy with lamivudine. However, the first muscle biopsy with large cytoplasmic vacuoles confused the diagnosis and led to the second biopsy that allowed for the final diagnosis. Patient B had severe cardiac disturbances leading to sudden death. Molecularly, patient A harbored a synonymous mutation adjacent to the exon 6-intron 6 junction; mRNA analysis provided evidence that totally abolished the donor site and caused skipping of exon 6. Patient B harbored a frame-shift deletion mutation in exon 3 (c.396delA) leading to a truncated protein.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of Danon disease caused by a synonymous exon mutation that affected mRNA splicing, which indicates that a synonymous substitution may not be silent when it is in the exon sequences close to the splice sites. It is also the first description of Danon disease clinically presenting as druginduced myopathy at onset; the pathological changes might be the key point for making a differential diagnosis. *These two authors contributed equally to this work.
authors.forename: Su-shan
authors.initials: SS
authors.lastname: Luo
authors.forename: Jian-ying
authors.initials: JY
authors.lastname: Xi
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.forename: Chong-bo
authors.initials: CB
authors.lastname: Zhao
authors.forename: Jia-hong
authors.initials: JH
authors.lastname: Lu
authors.forename: Wen-hua
authors.initials: WH
authors.lastname: Zhu
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Kai
authors.initials: K
authors.lastname: Qiao
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhu-rong
authors.initials: ZR
authors.lastname: Ye
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D052120:Glycogen Storage Disease Type IIb / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D052119:Lysosomal-Associated Membrane Protein 2 / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2