Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy

UMMS Affiliation

Howard Hughes Medical Institute, Program in Molecular Medicine

Publication Date


Document Type



Base Sequence; DNA Primers; DNA, Complementary; Gene Expression Regulation; Humans; Molecular Sequence Data; Muscle Proteins; Muscular Dystrophy, Facioscapulohumeral; Subtraction Technique


Life Sciences | Medicine and Health Sciences


Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by an insidious onset and progressive course. The disease has a frequency of about 1 in 20,000 and is transmitted in an autosomal dominant fashion with almost complete penetrance. Deletion of an integral number of tandemly arrayed 3.3-kb repeat units (D4Z4) on chromosome 4q35 is associated with FSHD but otherwise the molecular basis of the disease and its pathophysiology remain obscure. Comparison of mRNA populations between appropriate cell types can facilitate identification of genes relevant to a particular biological or pathological process. In this report, we have compared mRNA populations of FSHD and normal muscle. Unexpectedly, the dystrophic muscle displayed profound alterations in gene expression characterized by severe underexpression or overexpression of specific mRNAs. Intriguingly, many of the deregulated mRNAs are muscle specific. Our results suggest that a global misregulation of gene expression is the underlying basis for FSHD, distinguishing it from other forms of muscular dystrophy. The experimental approach used here is applicable to any genetic disorder whose pathogenic mechanism is incompletely understood.


Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12650-4.

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

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PubMed ID