BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions within a tandem array of D4Z4 repeats on chromosome 4q35. In addition to muscle degeneration, most patients with FSHD develop abnormalities of the retinal vasculature. Previous work has suggested that muscle degeneration in FSHD results from increased expression of genes proximal to the deletion, including FRG1. OBJECTIVES: To reexamine this mechanism and identify pathways that are abnormally regulated early in the disease process. METHODS: We prospectively studied gene expression in skeletal muscle in patients with FSHD (n = 19) vs healthy individuals (n = 30) and patients with myotonic dystrophy type 1 (n = 12). We used oligonucleotide microarrays for global analysis of gene expression and reverse transcriptase-PCR (RT-PCR) to assess expression or alternative splicing for particular genes. RESULTS: Expression of FRG1 was not increased in patients with FSHD, either by microarray analysis or quantitative RT-PCR. Among genes on 4q35, only LRP2BP showed upregulation that was specific to FSHD. However, neither LRP2BP nor FRG1 showed imbalance of allelic expression by RT-PCR. After filtering out genes that showed similar dysregulation in other forms of muscular dystrophy, only 44 genes were specifically upregulated early in FSHD. Among these, 34 genes were characterized or partially characterized, of which 11 (32%) had a role in vascular smooth muscle or endothelial cells. CONCLUSION: Expression of genes on chromosome 4q35 was normally regulated in the early stages of facioscapulohumeral muscular dystrophy. Our results support a possible link between muscular dystrophy and retinal vasculopathy in facioscapulohumeral muscular dystrophy.
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is caused by deletions within a tandem array of D4Z4 repeats on chromosome 4q35. In addition to muscle degeneration, most patients with FSHD develop abnormalities of the retinal vasculature. Previous work has suggested that muscle degeneration in FSHD results from increased expression of genes proximal to the deletion, including FRG1. OBJECTIVES: To reexamine this mechanism and identify pathways that are abnormally regulated early in the disease process. METHODS: We prospectively studied gene expression in skeletal muscle in patients with FSHD (n = 19) vs healthy individuals (n = 30) and patients with myotonic dystrophy type 1 (n = 12). We used oligonucleotide microarrays for global analysis of gene expression and reverse transcriptase-PCR (RT-PCR) to assess expression or alternative splicing for particular genes. RESULTS: Expression of FRG1 was not increased in patients with FSHD, either by microarray analysis or quantitative RT-PCR. Among genes on 4q35, only LRP2BP showed upregulation that was specific to FSHD. However, neither LRP2BP nor FRG1 showed imbalance of allelic expression by RT-PCR. After filtering out genes that showed similar dysregulation in other forms of muscular dystrophy, only 44 genes were specifically upregulated early in FSHD. Among these, 34 genes were characterized or partially characterized, of which 11 (32%) had a role in vascular smooth muscle or endothelial cells. CONCLUSION: Expression of genes on chromosome 4q35 was normally regulated in the early stages of facioscapulohumeral muscular dystrophy. Our results support a possible link between muscular dystrophy and retinal vasculopathy in facioscapulohumeral muscular dystrophy.
Authors: Petr Dmitriev; Andrei Petrov; Eugenie Ansseau; Luiza Stankevicins; Sébastien Charron; Elena Kim; Tomas Jan Bos; Thomas Robert; Ahmed Turki; Frédérique Coppée; Alexandra Belayew; Vladimir Lazar; Gilles Carnac; Dalila Laoudj; Marc Lipinski; Yegor S Vassetzky Journal: J Biol Chem Date: 2011-09-21 Impact factor: 5.157
Authors: Michael G Poulos; Ranjan Batra; Konstantinos Charizanis; Maurice S Swanson Journal: Cold Spring Harb Perspect Biol Date: 2011-01-01 Impact factor: 10.005
Authors: Petr Dmitriev; Luiza Stankevicins; Eugenie Ansseau; Andrei Petrov; Ana Barat; Philippe Dessen; Thomas Robert; Ahmed Turki; Vladimir Lazar; Emmanuel Labourer; Alexandra Belayew; Gilles Carnac; Dalila Laoudj-Chenivesse; Marc Lipinski; Yegor S Vassetzky Journal: J Biol Chem Date: 2013-10-20 Impact factor: 5.157
Authors: Yuanfan Zhang; Oliver D King; Fedik Rahimov; Takako I Jones; Christopher W Ward; Jaclyn P Kerr; Naili Liu; Charles P Emerson; Louis M Kunkel; Terence A Partridge; Kathryn R Wagner Journal: Hum Mol Genet Date: 2014-01-22 Impact factor: 6.150
Authors: Manjusha Dixit; Eugénie Ansseau; Alexandra Tassin; Sara Winokur; Rongye Shi; Hong Qian; Sébastien Sauvage; Christel Mattéotti; Anne M van Acker; Oberdan Leo; Denise Figlewicz; Marietta Barro; Dalila Laoudj-Chenivesse; Alexandra Belayew; Frédérique Coppée; Yi-Wen Chen Journal: Proc Natl Acad Sci U S A Date: 2007-11-05 Impact factor: 11.205