Danon disease: a novel LAMP2 mutation affecting the pre-mRNA splicing and causing aberrant transcripts and partial protein expression.

Abstract

LAMP2, the causative gene of Danon disease, located on chromosome Xq24, encodes the lysosome-associated membrane protein-2 (LAMP-2). We describe clinical features and molecular data in an Italian patient with Danon disease. The patient had hyperCKemia, hypertrophic cardiomyopathy, no muscle weakness and slight mental impairment. Muscle biopsy revealed autophagic vacuoles with sarcolemmal features and glycogen storage. Immunohistochemistry and immunoblot revealed traces of LAMP-2 protein in skeletal muscle. Molecular analysis of the LAMP2 gene revealed a novel hemizygous mutation affecting the invariant +1 position of the splice site of intron 8, resulting in aberrant transcripts with skipping of exon 8 in all three LAMP-2 isoforms, skipping of exons 7 and 8 in LAMP-2A and 2C, and a 15 bp deletion in exon 8 of LAMP-2B. Low levels of normal LAMP-2B transcript were also present. Danon disease is an under-recognized and frequently fatal condition, treatable by heart transplantation. Investigation of the primary molecular defect is important for cardiac surveillance and genetic counseling.

• Authors: Claudia Di Blasi, Laura Jarre, Flavia Blasevich, Patrizia Dassi, Marina Mora
• Journal: Neuromuscular disorders : NMD (Neuromuscul Disord) Vol. 18 Issue 12 Pg. 962-6 (Dec 2008) ISSN: 0960-8966 [Print] England
• PMID: 18990578 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• LAMP2 protein, human
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins
• RNA, Messenger

Topics

• Adolescent
• Base Sequence
• DNA Mutational Analysis (methods)
• Exons
• Glycogen Storage Disease Type IIb (genetics, metabolism, pathology)
• Humans
• Immunoblotting
• Lysosomal-Associated Membrane Protein 2
• Lysosome-Associated Membrane Glycoproteins (genetics, metabolism)
• Microscopy, Electron
• Muscle, Skeletal (metabolism, pathology, ultrastructure)
• Mutation
• RNA Splicing
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction