Abstract
Background:
X-linked myotubular myopathy (XLMTM) is a severe congenital disorder characterized by marked muscle weakness and hypotonia. Myotubularin, the protein product of the causative gene, MTM1, is thought to be a phosphatase for phosphatidylinositol-3-phosphate and may be involved in membrane trafficking. Analysis of MTM1 knocked-out mice indicates that the characteristic small fibers in XLMTM muscles are due to atrophy rather than hypoplasia.
Objective:
To characterize gene expression profiling of skeletal muscles with XLMTM.
Method:
The authors analyzed the expression of more than 4,200 genes in skeletal muscles from eight patients with XLMTM using their custom cDNA microarray.
Results:
In XLMTM, gene expression analysis revealed pathognomonic upregulation of transcripts for cytoskeletal and extracellular matrix proteins within or around atrophic myofibers.
Conclusion:
Remodeling of cytoskeletal and extracellular architecture appears to contribute to atrophy and intracellular organelle disorganization in XLMTM myofibers.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Cytoskeleton / genetics
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Cytoskeleton / metabolism
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Cytoskeleton / pathology
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Extracellular Matrix / genetics
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Extracellular Matrix / metabolism
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Extracellular Matrix / pathology
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Extracellular Matrix Proteins / genetics
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Gene Expression Profiling
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Gene Expression Regulation, Developmental / genetics*
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Genetic Diseases, X-Linked / genetics*
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Genetic Predisposition to Disease / genetics*
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Humans
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Immunohistochemistry
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Infant
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Infant, Newborn
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Muscle Fibers, Skeletal / metabolism
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Muscle Fibers, Skeletal / pathology
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Muscle, Skeletal / metabolism*
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Muscle, Skeletal / pathology
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Muscle, Skeletal / physiopathology
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Muscular Atrophy / genetics
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Muscular Atrophy / metabolism
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Muscular Atrophy / physiopathology
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Myopathies, Structural, Congenital / genetics*
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Myopathies, Structural, Congenital / metabolism
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Myopathies, Structural, Congenital / physiopathology
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Up-Regulation / genetics
Substances
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Cytoskeletal Proteins
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Extracellular Matrix Proteins
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RNA, Messenger