1,261 results match your criteria Facioscapulohumeral Dystrophy


Digenic Inheritance of Shortened Repeat Units of the D4Z4 Region and a Loss-of-Function Variant in in a Family With FSHD.

Front Neurol 2018 28;9:1027. Epub 2018 Nov 28.

Molecular Genetics Laboratory UILDM, Santa Lucia Foundation, Rome, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder which is typically transmitted by an autosomal dominant pattern, although reduced penetrance and sporadic cases caused by mutations, are often observed. FSHD may be caused by a contraction of a repetitive element, located on chromosome 4 (4q35). This locus is named and consists of 11 to more than 100 repeated units (RU). Read More

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http://dx.doi.org/10.3389/fneur.2018.01027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279899PMC
November 2018

Human iPSC Models to Study Orphan Diseases: Muscular Dystrophies.

Curr Stem Cell Rep 2018 4;4(4):299-309. Epub 2018 Oct 4.

3Houston Methodist Neurological Institute and Research Institute, 6670 Bertner Ave R11-117, Houston, TX USA.

Purpose Of Review: Muscular dystrophies (MDs) are a spectrum of muscle disorders, which are caused by a number of gene mutations. The studies of MDs are limited due to lack of appropriate models, except for Duchenne muscular dystrophy (DMD), myotonic dystrophy type 1 (DM1), facioscapulohumeral muscular dystrophy (FSHD), and certain type of limb-girdle muscular dystrophy (LGMD). Human induced pluripotent stem cell (iPSC) technologies are emerging to offer a useful model for mechanistic studies, drug discovery, and cell-based therapy to supplement in vivo animal models. Read More

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http://dx.doi.org/10.1007/s40778-018-0145-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6244555PMC
October 2018

Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.

Cell Rep 2018 Dec;25(11):2955-2962.e3

Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:

Double homeobox (DUX) transcription factors are unique to eutherian mammals. DUX4 regulates expression of repetitive elements during early embryogenesis, but misexpression of DUX4 causes facioscapulohumeral muscular dystrophy (FSHD) and translocations overexpressing the DUX4 double homeodomain cause B cell leukemia. Here, we report the crystal structure of the tandem homeodomains of DUX4 bound to DNA. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247183183
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http://dx.doi.org/10.1016/j.celrep.2018.11.060DOI Listing
December 2018
3 Reads

Acupuncture improves the facial muscular function in a case of facioscapulohumeral muscular dystrophy.

J Acupunct Meridian Stud 2018 Nov 30. Epub 2018 Nov 30.

Department of Neurology and Neurological Sciences, Stanford University, Stanford, 94305 USA. Electronic address:

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic muscle disorder in which muscles of the face, shoulder blades and upper arms develop gradual and progressive weakness. There is no effective pharmacological treatment currently available for this disorder so far. We had an opportunity to treat a patient with FSHD using acupuncture. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S20052901163025
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http://dx.doi.org/10.1016/j.jams.2018.11.001DOI Listing
November 2018
2 Reads

The French National Registry of patients with Facioscapulohumeral muscular dystrophy.

Orphanet J Rare Dis 2018 Dec 4;13(1):218. Epub 2018 Dec 4.

Aix Marseille Univ, INSERM, MMG, Bioinformatics & Genetics, Marseille, France.

Background: Facioscapulohumeral muscular dystrophy is a rare inherited neuromuscular disease with an estimated prevalence of 1/20,000 and France therefore harbors about 3000 FSHD patients. With research progress and the development of targeted therapies, patients' identification through registries can facilitate and improve recruitment in clinical trials and studies.

Results: The French National Registry of FSHD patients was designed as a mixed model registry involving both patients and physicians, through self-report and clinical evaluation questionnaires respectively, to collect molecular and clinical data. Read More

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http://dx.doi.org/10.1186/s13023-018-0960-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280451PMC
December 2018
1 Read

Dynamic transcriptomic analysis reveals suppression of PGC1α/ERRα drives perturbed myogenesis in facioscapulohumeral muscular dystrophy.

Hum Mol Genet 2018 Dec 6. Epub 2018 Dec 6.

King's College London, Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, London SE1 1UL, UK.

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to epigenetic de-repression of D4Z4 repeats on chromosome 4q, leading to ectopic DUX4 expression. FSHD patient myoblasts have defective myogenic differentiation, forming smaller myotubes with reduced myosin content. However, molecular mechanisms driving such disrupted myogenesis in FSHD are poorly understood. Read More

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http://dx.doi.org/10.1093/hmg/ddy405DOI Listing
December 2018
19 Reads

Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression.

Sci Rep 2018 Nov 16;8(1):16957. Epub 2018 Nov 16.

Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, 55455, USA.

Loss of silencing of the DUX4 gene on chromosome 4 causes facioscapulohumeral muscular dystrophy. While high level DUX4 expression induces apoptosis, the effects of low level DUX4 expression on human myogenic cells are not well understood. Low levels and sporadic expression of DUX4 have been reported in FSHD biopsy samples and myoblast cultures. Read More

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http://www.nature.com/articles/s41598-018-35150-8
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http://dx.doi.org/10.1038/s41598-018-35150-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240038PMC
November 2018
3 Reads

Single-cell RNA-sequencing in facioscapulohumeral muscular dystrophy disease etiology and development.

Hum Mol Genet 2018 Nov 16. Epub 2018 Nov 16.

Department of Human Genetics, Leiden University Medical Center, 2333 ZC Leiden, Zuid-Holland, The Netherlands.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by sporadic de-repression of the transcription factor DUX4 in skeletal muscle. DUX4 activates a cascade of muscle disrupting events, eventually leading to muscle atrophy and apoptosis. Yet, how sporadic DUX4 expression leads to the generalized muscle wasting remains unclear. Read More

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http://fdslive.oup.com/www.oup.com/pdf/production_in_progres
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http://dx.doi.org/10.1093/hmg/ddy400DOI Listing
November 2018
5 Reads

AAV-mediated follistatin gene therapy improves functional outcomes in the TIC-DUX4 mouse model of FSHD.

JCI Insight 2018 Nov 15;3(22). Epub 2018 Nov 15.

Biomedical Sciences Graduate Program, The Ohio State University, Columbus, Ohio, USA.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant or digenic disorder linked to derepression of the toxic DUX4 gene in muscle. There is currently no pharmacological treatment. The emergence of DUX4 enabled development of cell and animal models that could be used for basic and translational research. Read More

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https://insight.jci.org/articles/view/123538
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http://dx.doi.org/10.1172/jci.insight.123538DOI Listing
November 2018
6 Reads

Isokinetic assessment of trunk muscles in facioscapulohumeral muscular dystrophy type 1 patients.

Neuromuscul Disord 2018 Dec 27;28(12):996-1002. Epub 2018 Sep 27.

Hôpital Rothschild, Service de Reeducation Neuro-orthopédique, 5 Rue Santerre 75012 Paris, France.

Facioscapulohumeral muscular dystrophy type 1 is the third most common inherited myopathy. Its severity is proportionate to the loss of microsatellite D4Z4 repetitions, which are below 10. Patients suffer from weakness in facial muscles, shoulder girdles and ankle dorsiflexors. Read More

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http://dx.doi.org/10.1016/j.nmd.2018.09.007DOI Listing
December 2018

Facioscapulohumeral Muscular Dystrophy: Update on Pathogenesis and Future Treatments.

Neurotherapeutics 2018 Oct;15(4):863-871

Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 673, Rochester, NY, 14642, USA.

A reliable model of a disease pathomechanism is the first step to develop targeted treatment. In facioscapulohumeral muscular dystrophy (FSHD), the third most common muscular dystrophy, recent advances in understanding the complex genetics and epigenetics have led to the identification of a disease mechanism, moving the field towards targeted therapy development. FSHD is caused by expression of DUX4, a retrogene located on the D4Z4 macrosatellite repeat array on chromosome 4q35, a gene expressed in the germline but typically repressed in somatic tissue. Read More

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http://dx.doi.org/10.1007/s13311-018-00675-3DOI Listing
October 2018

Experiences with bariatric surgery in patients with facioscapulohumeral dystrophy and myotonic dystrophy type 1: A qualitative study.

Neuromuscul Disord 2018 Nov 19;28(11):938-946. Epub 2018 Sep 19.

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Overweight and obesity are common in patients with facioscapulohumeral dystrophy (FSHD) and myotonic dystrophy type 1 (DM1). Lifestyle change is often challenging for patients with neuromuscular diseases, especially to increase physical activity. When lifestyle changes have not been effective, bariatric surgery is a treatment option. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09608966183102
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http://dx.doi.org/10.1016/j.nmd.2018.09.003DOI Listing
November 2018
6 Reads

Relationships between muscle size, strength, and physical activity in adults with muscular dystrophy.

J Cachexia Sarcopenia Muscle 2018 Dec 19;9(6):1042-1052. Epub 2018 Oct 19.

Research Centre for Musculoskeletal Science and Sports Medicine, School of Healthcare Science, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.

Background: Muscular dystrophy (MD) is characterized by progressive muscle wasting and weakness, yet few comparisons to non-MD controls (CTRL) of muscle strength and size in this adult population exist. Physical activity (PA) is promoted to maintain health and muscle strength within MD; however, PA reporting in adults with MD is limited to recall data, and its impact on muscle strength is seldom explored.

Methods: This study included 76 participants: 16 non-MD (CTRL, mean age 35. Read More

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http://doi.wiley.com/10.1002/jcsm.12347
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http://dx.doi.org/10.1002/jcsm.12347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240748PMC
December 2018
9 Reads

A multidisciplinary clinical approach to facioscapulohumeral muscular dystrophy.

Ideggyogy Sz 2018 Sep;71(9-10):337-342

Koç University, School of Medicine, Department of Neurology, Istanbul, Turkey.

Background And Purpose: Impaired shoulder function is the most disabling problem for daily life of Fascioscapulohumeral muscular dystrophy (FSHD) patients. Scapulothoracic arthrodesis can give a high impact to the functionality of patients. Here we report our experience with scapulothoracic arthrodesis and spinal stenosis surgery in FSHD patients. Read More

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http://elitmed.hu/kiadvanyaink/ideggyogyaszati-szemle/a-faci
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http://dx.doi.org/10.18071/isz.71.0337DOI Listing
September 2018
3 Reads

Different clinicopathological features between Japanese siblings with facioscapulohumeral muscular dystrophy 2 with a novel nonsense SMCHD1 mutation (Arg552).

J Clin Neurosci 2018 Dec 13;58:215-217. Epub 2018 Oct 13.

Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address:

Facioscapulohumeral muscular dystrophy (FSHD) 2 is caused by a combination of heterozygous structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) mutation plus DNA hypomethylation on D4Z4. Here we report two Japanese FSHD2 siblings (brother and sister) with a new SMCHD1 nonsense mutation (a heterogeneous c. 1654C > T substitution, leading to a stop codon Arg552). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09675868183074
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http://dx.doi.org/10.1016/j.jocn.2018.10.021DOI Listing
December 2018
4 Reads
1.320 Impact Factor

Structural basis for multiple gene regulation by human DUX4.

Biochem Biophys Res Commun 2018 Nov 12;505(4):1161-1167. Epub 2018 Oct 12.

State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Shanghai, 200438, China. Electronic address:

DUX4 plays critical role in the molecular pathogenesis of the neuromuscular disorder facioscapulohumeral muscular dystrophy and acute lymphoblastic leukemia in humans. As a master transcription regulator, DUX4 can also bind the promoters and activate the transcription of hundreds ZGA-associated genes. Here we report on the structural and biochemical studies of DUX4 double homeodomains (DUX4-DH), representing the only structures contain both homeodomain 1 (HD1) and homeodomain 2 (HD2). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0006291X183220
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http://dx.doi.org/10.1016/j.bbrc.2018.10.056DOI Listing
November 2018
6 Reads

MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD.

Hum Mol Genet 2018 Oct 12. Epub 2018 Oct 12.

Neuromuscular Unit, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.

Facioscapulohumeral muscular dystrophy (FSHD) is a common, dominantly inherited disease caused by the epigenetic de-repression of the DUX4 gene, a transcription factor normally repressed in skeletal muscle. As targeted therapies are now possible in FSHD, a better understanding of the relationship between DUX4 activity, muscle pathology and muscle MRI changes are crucial both to understand disease mechanisms and for the design of future clinical trials. Here, we performed MRIs of the lower extremities in 36 individuals with FSHD, followed by needle muscle biopsies in safely accessible muscles. Read More

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https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg
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http://dx.doi.org/10.1093/hmg/ddy364DOI Listing
October 2018
6 Reads
6.390 Impact Factor

Transgenic zebrafish model of DUX4 misexpression reveals a developmental role in FSHD pathogenesis.

Hum Mol Genet 2018 10 10. Epub 2018 Oct 10.

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.

Facioscapulohumeral dystrophy Type 1 (FSHD-1) is the most common autosomal dominant form of muscular dystrophy with a prevalence of approximately 1 in 8,000 individuals. It is considered a late-onset form of muscular dystrophy and leads to asymmetric muscle weakness in the facial, scapular, trunk and lower extremities. The prevalent hypothesis on disease pathogenesis is explained by misexpression of a germline, primate specific transcription factor DUX4-fl (double homeo-box 4, full-length isoform) linked to the chromosome 4q35. Read More

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https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg
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http://dx.doi.org/10.1093/hmg/ddy348DOI Listing
October 2018
1 Read

Cis D4Z4 repeat duplications associated with facioscapulohumeral muscular dystrophy type 2.

Hum Mol Genet 2018 Oct;27(20):3488-3497

Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.

Facioscapulohumeral muscular dystrophy, known in genetic forms FSHD1 and FSHD2, is associated with D4Z4 repeat array chromatin relaxation and somatic derepression of DUX4 located in D4Z4. A complete copy of DUX4 is present on 4qA chromosomes, but not on the D4Z4-like repeats of chromosomes 4qB or 10. Normally, the D4Z4 repeat varies between 8 and 100 units, while in FSHD1 it is only 1-10 units. Read More

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https://academic.oup.com/hmg/article/27/20/3488/5042899
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http://dx.doi.org/10.1093/hmg/ddy236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168970PMC
October 2018
1 Read

A case of facioscapulohumeral muscular dystrophy and myasthenia gravis with positivity of anti-Ach receptor antibody: a fortuitous association?

Neurol Sci 2018 Sep 13. Epub 2018 Sep 13.

Institute of Neurology, University Magna Graecia of Catanzaro, Germaneto, Catanzaro, Italy.

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http://dx.doi.org/10.1007/s10072-018-3554-4DOI Listing
September 2018

Phenotype-genotype relations in facioscapulohumeral muscular dystrophy type 1.

Clin Genet 2018 Dec 8;94(6):521-527. Epub 2018 Oct 8.

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.

To determine how much of the clinical variability in facioscapulohumeral muscular dystrophy type 1 (FSHD1) can be explained by the D4Z4 repeat array size, D4Z4 methylation and familial factors, we included 152 carriers of an FSHD1 allele (23 single cases, 129 familial cases from 37 families) and performed state-of-the-art genetic testing, extensive clinical evaluation and quantitative muscle MRI. Familial factors accounted for 50% of the variance in disease severity (FSHD clinical score). The explained variance by the D4Z4 repeat array size for disease severity was limited (approximately 10%), and varied per body region (facial muscles, upper and lower extremities approximately 30%, 15% and 3%, respectively). Read More

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http://dx.doi.org/10.1111/cge.13446DOI Listing
December 2018

A "Triple Trouble" Case of Facioscapulohumeral Muscular Dystrophy Accompanied by Peripheral Neuropathy and Myoclonic Epilepsy.

Chin Med J (Engl) 2018 Sep;131(18):2164-2171

Department of Neurology and Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, China.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric muscular deficit of facial, shoulder-girdle muscles, and descending to lower limb muscles, but it exists in several extramuscular manifestations or overlapping syndromes. Herein, we report a "complex disease plus" patient with FSHD1, accompanied by peripheral neuropathy and myoclonic epilepsy.

Methods: Standard clinical assessments, particular auxiliary examination, histological analysis, and molecular analysis were performed through the new Comprehensive Clinical Evaluation Form, pulsed-field gel electrophoresis-based Southern blot, Multiplex Ligation-dependent Probe Amplification (MLPA), whole exome sequencing (WES), and targeted methylation sequencing. Read More

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http://dx.doi.org/10.4103/0366-6999.240797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144853PMC
September 2018
11 Reads

Quantitative muscle MRI and ultrasound for facioscapulohumeral muscular dystrophy: complementary imaging biomarkers.

J Neurol 2018 Nov 6;265(11):2646-2655. Epub 2018 Sep 6.

Department of Neurology and Clinical Neurophysiology, Radboud University Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.

Objective: To assess the overlap of and differences between quantitative muscle MRI and ultrasound in characterizing structural changes in leg muscles of facioscapulohumeral muscular dystrophy (FSHD) patients.

Methods: We performed quantitative MRI and quantitative ultrasound of ten leg muscles in 27 FSHD patients and assessed images, both quantitatively and visually, for fatty infiltration, fibrosis and edema.

Results: The MRI fat fraction and ultrasound echogenicity z-score correlated strongly (CC 0. Read More

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http://dx.doi.org/10.1007/s00415-018-9037-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182682PMC
November 2018

Facioscapulohumeral Dystrophy in Childhood: A Nationwide Natural History Study.

Ann Neurol 2018 Nov 16;84(5):627-637. Epub 2018 Oct 16.

Department of Neurology, Donders Centre for Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.

Objective: Facioscapulohumeral dystrophy (FSHD) is one of the most frequent heritable muscular dystrophies, with a large variety in age at onset and disease severity. The natural history and molecular characteristics of FSHD in childhood are incompletely understood. Our objective is to clinically and genetically characterize FSHD in childhood. Read More

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http://doi.wiley.com/10.1002/ana.25326
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http://dx.doi.org/10.1002/ana.25326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282793PMC
November 2018
23 Reads

Antisense Oligonucleotide Targeting of 3'-UTR of mRNA for Expression Knockdown.

Methods Mol Biol 2018 ;1828:91-124

Centre of Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey, UK.

With the recent conditional approval of an antisense oligonucleotide (AON) that restores the reading frame of DMD transcript in a subset of Duchenne muscular dystrophy patients, it has been established that AONs sharing similar chemistry have clear clinical potential. Genetic diseases, such as facioscapulohumeral dystrophy (FSHD), can be the result of gain-of-function mutations. Since mRNA processing in terms of termination of transcription, its transport from the nucleus to the cytoplasm, its stability and translation efficiency are dependent on key 3'UTR elements, it follows that targeting these elements with AONs have the potential to induce gene silencing. Read More

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http://dx.doi.org/10.1007/978-1-4939-8651-4_6DOI Listing
January 2018
4 Reads

[Innovative therapeutic approaches for hereditary neuromuscular diseases].

Nervenarzt 2018 Oct;89(10):1115-1122

Friedrich-Baur-Institut, Neurologische Klinik und Poliklinik, Ludwig-Maximilians-Universität München, München, Deutschland.

Advances in the understanding of the genetic mechanisms and pathophysiology of neuromuscular diseases have recently led to the development of new, innovative and often mutation-specific therapeutic approaches. Methods used include splicing modification by antisense oligonucleotides, read-through of premature stopcodons, use of viral vectors to introduce genetic information, or optimizing the effectiveness of enzyme replacement therapies. The first drugs have already been approved for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy. Read More

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http://dx.doi.org/10.1007/s00115-018-0599-9DOI Listing
October 2018

Sporadic DUX4 expression in FSHD myocytes is associated with incomplete repression by the PRC2 complex and gain of H3K9 acetylation on the contracted D4Z4 allele.

Epigenetics Chromatin 2018 08 20;11(1):47. Epub 2018 Aug 20.

Departments of Pediatrics and Genome Sciences, University of Washington, Seattle, WA, USA.

Background: Facioscapulohumeral muscular dystrophy 1 (FSHD1) has an autosomal dominant pattern of inheritance and primarily affects skeletal muscle. The genetic cause of FSHD1 is contraction of the D4Z4 macrosatellite array on chromosome 4 alleles associated with a permissive haplotype causing infrequent sporadic expression of the DUX4 gene. Epigenetically, the contracted D4Z4 array has decreased cytosine methylation and an open chromatin structure. Read More

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http://dx.doi.org/10.1186/s13072-018-0215-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100714PMC

A patient-derived iPSC model revealed oxidative stress increases facioscapulohumeral muscular dystrophy-causative DUX4.

Hum Mol Genet 2018 Dec;27(23):4024-4035

Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.

Double homeobox 4 (DUX4), the causative gene of facioscapulohumeral muscular dystrophy (FSHD), is ectopically expressed in the skeletal muscle cells of FSHD patients because of chromatin relaxation at 4q35. The diminished heterochromatic state at 4q35 is caused by either large genome contractions [FSHD type 1 (FSHD1)] or mutations in genes encoding chromatin regulators, such as SMCHD1 [FSHD type 2 (FSHD2)]. However, the mechanism by which DUX4 expression is regulated remains largely unknown. Read More

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https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg
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http://dx.doi.org/10.1093/hmg/ddy293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240734PMC
December 2018
7 Reads
6.393 Impact Factor

MRI-Guided Biopsy as a Tool for Diagnosis and Research of Muscle Disorders.

J Neuromuscul Dis 2018;5(3):315-319

Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, The Netherlands.

Background: Sampling error is a common problem in muscle biopsies. MRI-guided biopsy allows verification of biopsy site during the procedure, which may reduce sampling error in patients with focal disease.

Objectives: To describe the technique for MRI-guided muscle biopsy and discuss potential applications. Read More

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http://dx.doi.org/10.3233/JND-180318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087442PMC
November 2018

Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage.

Skelet Muscle 2018 08 2;8(1):24. Epub 2018 Aug 2.

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA.

Background: SMCHD1 is a disease modifier and a causative gene for facioscapulohumeral muscular dystrophy (FSHD) type 1 and type 2, respectively. A large variety of different mutations in SMCHD1 have been identified as causing FSHD2. In many cases, it is unclear how these mutations disrupt the normal function of SMCHD1. Read More

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http://dx.doi.org/10.1186/s13395-018-0172-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090946PMC
August 2018
7 Reads

Muscular Dystrophy Surveillance, Tracking, and Research Network pilot: Population-based surveillance of major muscular dystrophies at four U.S. sites, 2007-2011.

Birth Defects Res 2018 Nov 2;110(19):1404-1411. Epub 2018 Aug 2.

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities, Atlanta, Georgia.

Background: For 10 years, the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet) conducted surveillance for Duchenne and Becker muscular dystrophy (DBMD). We piloted expanding surveillance to other MDs that vary in severity, onset, and sources of care.

Methods: Our retrospective surveillance included individuals diagnosed with one of nine eligible MDs before or during the study period (January 2007-December 2011), one or more health encounters, and residence in one of four U. Read More

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http://dx.doi.org/10.1002/bdr2.1371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265066PMC
November 2018
3 Reads

Atypical presentation of Coats' Syndrome in facioscapulohumeral dystrophy - Reflecting the variation in phenotypic manifestations.

Am J Ophthalmol Case Rep 2018 Sep 21;11:17-18. Epub 2018 Apr 21.

Brighton and Sussex University Hospitals NHS Trust, Sussex Eye Hospital, Eastern Road, Brighton, BN2 5BF, United Kingdom.

Purpose: To report a unique case of atypical Coats' Syndrome in an 80 year old female with facioscapulohumeral dystrophy.

Observations: An 80 years old female was diagnosed clinically of retinal telangiectasia with exudation threatening the fovia. She received a successful macular laser photocoagulation with subsequent cessation of leakage. Read More

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http://dx.doi.org/10.1016/j.ajoc.2018.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061899PMC
September 2018

Inflammatory facioscapulohumeral muscular dystrophy type 2 in 18p deletion syndrome.

Am J Med Genet A 2018 Aug 28;176(8):1760-1763. Epub 2018 Jul 28.

Peripheral Nervous System, Muscle and ALS Department, Nice University Hospital, Université Côte d'Azur, Nice, France.

Facioscapulohumeral muscular dystrophy (FSHD) has been shown to be related to genetic and epigenetic derepression of DUX4 (mapping to chromosome 4), a gene located within a repeat array of D4Z4 sequences of polymorphic length. FSHD type 1 (FSHD1) is associated with pathogenic D4Z4 repeat array contraction, while FSHD type 2 (FSHD2) is associated with SMCHD1 variants (a chromatin modifier gene that maps to the short arm of chromosome 18). Both FSHD types require permissive polyadenylation signal (4qA) downstream of the D4Z4 array. Read More

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http://doi.wiley.com/10.1002/ajmg.a.38843
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http://dx.doi.org/10.1002/ajmg.a.38843DOI Listing
August 2018
10 Reads
2.160 Impact Factor

Exercise in muscle disorders: what is our current state?

Curr Opin Neurol 2018 Oct;31(5):610-617

Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Purpose Of Review: Regular exercise improves muscle and cardiovascular function, which is why exercise is used as an adjuvant treatment in myopathies. In this review, we provide an update on recent exercise studies (from 2016) performed in humans with inherited myopathy.

Recent Findings: Several studies provide new and interesting insight in the field of exercise in myopathies. Read More

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http://dx.doi.org/10.1097/WCO.0000000000000597DOI Listing
October 2018
6 Reads

A family-based study into penetrance in facioscapulohumeral muscular dystrophy type 1.

Neurology 2018 Jul 11;91(5):e444-e454. Epub 2018 Jul 11.

From the Department of Neurology (M.W., C.G.H., B.G.v.E., G.W.P., N.C.V.), Donders Institute for Brain, Cognition and Behavior, and Radboud Institute for Health Sciences (M.J.), Radboud University Medical Center, Nijmegen; Department of Neurology (M.W.), ETZ, Tilburg; Department of Human Genetics (R.J.L., S.M.v.d.M.), Leiden University Medical Center; and Department of Neurology (E.v.d.K.), MCL, Leeuwarden, the Netherlands.

Objective: An observational cross-sectional study was conducted in a national facioscapulohumeral muscular dystrophy (FSHD) expertise center to estimate the penetrance of FSHD1 and to evaluate phenotype-genotype correlations.

Methods: Ten FSHD1 probands carrying 4-9 D4Z4 unit alleles and 140 relatives were examined. All 150 participants were genetically characterized, including D4Z4 methylation levels in the mutation carriers. Read More

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http://dx.doi.org/10.1212/WNL.0000000000005915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093768PMC
July 2018
3 Reads

FSHD type 2 and Bosma arhinia microphthalmia syndrome: Two faces of the same mutation.

Neurology 2018 Aug 6;91(6):e562-e570. Epub 2018 Jul 6.

From the Department of Neurology (K.M., N.C.V., B.G.M.v.E., C.G.C.H.), Radboud University Medical Center, Nijmegen; Departments of Human Genetics (R.J.L.F.L., P.J.v.d.V., M.L.v.d.B., S.M.v.d.M.), Clinical Genetics (M.K.), and Neurology (U.A.B.), Leiden University Medical Center, Leiden, the Netherlands; Department of Pediatrics (J.M.G.), Cedars Sinai Medical Center, Los Angeles, CA; Department of Medical Genetics (A.E.L.), MassGeneral Hospital for Children, Boston, MA; Center for Genomic Medicine and Department of Neurology (H.B.), Massachusetts General Hospital, Boston; Department of Pathology (S.A.M.), University of Iowa Hospitals and Clinics, Iowa City; The John Walton Muscular Dystrophy Research Centre (K.J., T.E., A.T., V.S.), Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; Neuromuscular Consult Unit (S.K.G.), Bilbo-Basurtu Erakunde Sanitario Integratua, Organización Sanitaria Integrada Bilbao-Basurto, Spain; Centre de Référence des Maladies Neuromusculaires (S.S.), Nice, France; Department of Neurology (R.T.), University of Rochester Medical Center, NY; Division of Human Biology (S.J.T.), Fred Hutchinson Cancer Research Center, Seattle, WA; and National Institute of Environmental Health Sciences (N.D.S.), Research Triangle Park, NC.

Objective: To determine whether congenital arhinia/Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy type 2 (FSHD2), 2 seemingly unrelated disorders both caused by heterozygous pathogenic missense variants in the gene, might represent different ends of a broad single phenotypic spectrum associated with SMCHD1 dysfunction.

Methods: We examined and/or interviewed 14 patients with FSHD2 and 4 unaffected family members with N-terminal pathogenic missense variants to identify BAMS subphenotypes.

Results: None of the patients with FSHD2 or family members demonstrated any congenital defects or dysmorphic features commonly found in patients with BAMS. Read More

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http://dx.doi.org/10.1212/WNL.0000000000005958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105048PMC
August 2018
12 Reads

Long-term results of scapulothoracic arthrodesis with multiple cable method for facioscapulohumeral dystrophy.

Bone Joint J 2018 07;100-B(7):953-956

Department of Orthopaedics and Traumatology, KOÇ University School of Medicine, Istanbul, Turkey.

Aims: The present study aimed to investigate the long-term functional results of scapulothoracic fusion using multifilament cables in patients with facioscapulohumeral dystrophy (FSHD) to identify if the early improvement from this intervention is maintained.

Patients And Methods: We retrospectively investigated the long-term outcomes of 13 patients with FSHD (18 shoulders) in whom scapulothoracic fusion using multifilament cables was performed between 2004 and 2007. These patients have previously been reported at a mean of 35. Read More

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https://online.boneandjoint.org.uk/doi/10.1302/0301-620X.100
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http://dx.doi.org/10.1302/0301-620X.100B7.BJJ-2017-1438.R1DOI Listing
July 2018
6 Reads

Novel key roles for structural maintenance of chromosome flexible domain containing 1 (Smchd1) during preimplantation mouse development.

Mol Reprod Dev 2018 Jul;85(7):635-648

Department of Animal Science, Michigan State University, East Lansing, Michigan.

Structural maintenance of chromosome flexible domain containing 1 (Smchd1) is a chromatin regulatory gene for which mutations are associated with facioscapulohumeral muscular dystrophy and arhinia. The contribution of oocyte- and zygote-expressed SMCHD1 to early development was examined in mice ( Mus musculus) using a small interfering RNA knockdown approach. Smchd1 knockdown compromised long-term embryo viability, with reduced embryo nuclear volumes at the morula stage, reduced blastocyst cell number, formation and hatching, and reduced viability to term. Read More

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http://doi.wiley.com/10.1002/mrd.23001
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http://dx.doi.org/10.1002/mrd.23001DOI Listing
July 2018
9 Reads

Protein kinase A activation inhibits gene expression in myotubes from patients with facioscapulohumeral muscular dystrophy.

J Biol Chem 2018 Jul 13;293(30):11837-11849. Epub 2018 Jun 13.

From Musculoskeletal Diseases and

Facioscapulohumeral muscular dystrophy (FSHD) is among the most prevalent of the adult-onset muscular dystrophies. FSHD causes a loss of muscle mass and function, resulting in severe debilitation and reduction in quality of life. Currently, only the symptoms of FSHD can be treated, and such treatments have minimal benefit. Read More

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http://dx.doi.org/10.1074/jbc.RA118.002633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066320PMC
July 2018
4 Reads

Isoprostanes as markers for muscle aging in older athletes.

Biochim Open 2018 Jun 15;6:1-8. Epub 2017 Dec 15.

Institute of Metabolic and Cardiovascular Diseases, Joint Research Unit 1048 INSERM Adipolab Unit - Paul Sabatier University, Toulouse, France.

Introduction: Production of isoprostanes (IsoPs) is enhanced after acute, intense, and prolonged exercise, in untrained subjects. This effect is greater in older subjects. The present study aims to delineate the profile of acute-exercise-induced IsoPs levels in young and older endurance-trained subjects. Read More

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http://dx.doi.org/10.1016/j.biopen.2017.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991887PMC
June 2018
14 Reads

Muscular Dystrophies.

Clin Chest Med 2018 Jun;39(2):377-389

Division of Pediatric Pulmonology, MetroHealth Medical Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Drive, Cleveland, OH 44019, USA. Electronic address:

Muscular dystrophies represent a complex, varied, and important subset of neuromuscular disorders likely to require the care of a pulmonologist. The spectrum of conditions encapsulated by this subset ranges from severe and fatal congenital muscular dystrophies with onset in infancy to mild forms of limb and girdle weakness with onset in adulthood and minimal respiratory compromise. The list and classification of muscular dystrophies are undergoing near-constant revision, based largely on new insights from genetics and molecular medicine. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02725231183000
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http://dx.doi.org/10.1016/j.ccm.2018.01.004DOI Listing
June 2018
6 Reads

Identification of Epigenetic Regulators of DUX4-fl for Targeted Therapy of Facioscapulohumeral Muscular Dystrophy.

Mol Ther 2018 Jul 26;26(7):1797-1807. Epub 2018 Apr 26.

Department of Pharmacology, University of Nevada, Reno, School of Medicine, Reno, NV 89557, USA; Department of Cell and Developmental Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address:

Facioscapulohumeral muscular dystrophy (FSHD) is caused by epigenetic de-repression of the disease locus, leading to pathogenic misexpression of the DUX4 gene in skeletal muscle. While the factors and pathways involved in normal repression of the FSHD locus in healthy cells have been well characterized, very little is known about those responsible for the aberrant activation of DUX4-fl in FSHD myocytes. Reasoning that DUX4-fl activators might represent useful targets for small molecule inhibition, we performed a highly targeted, candidate-based screen of epigenetic regulators in primary FSHD myocytes. Read More

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http://dx.doi.org/10.1016/j.ymthe.2018.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6035737PMC
July 2018
3 Reads

A 22-year follow-up reveals a variable disease severity in early-onset facioscapulohumeral dystrophy.

Eur J Paediatr Neurol 2018 Sep 3;22(5):782-785. Epub 2018 May 3.

Department of Neurology, Radboud University Medical Centre, Nijmegen, The Netherlands.

Aim: To assess the long-term natural course of early-onset facioscapulohumeral dystrophy (FSHD), which is important for patient management and trial-readiness, and is currently lacking.

Methods: We had the unique opportunity to evaluate 10 patients with early-onset FSHD after 22 years follow-up. Patients underwent a semi-structured interview, physical examination and additional genotyping. Read More

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http://dx.doi.org/10.1016/j.ejpn.2018.04.013DOI Listing
September 2018
4 Reads

Targeting the Polyadenylation Signal of Pre-mRNA: A New Gene Silencing Approach for Facioscapulohumeral Dystrophy.

Int J Mol Sci 2018 May 3;19(5). Epub 2018 May 3.

NIHR Biomedical Research Centre, University College London, Great Ormond Street Institute of Child Health and Great Ormond Street Hospital NHS Trust, London WC1N 1EH, UK.

Facioscapulohumeral dystrophy (FSHD) is characterized by the contraction of the D4Z4 array located in the sub-telomeric region of the chromosome 4, leading to the aberrant expression of the DUX4 transcription factor and the mis-regulation of hundreds of genes. Several therapeutic strategies have been proposed among which the possibility to target the polyadenylation signal to silence the causative gene of the disease. Indeed, defects in mRNA polyadenylation leads to an alteration of the transcription termination, a disruption of mRNA transport from the nucleus to the cytoplasm decreasing the mRNA stability and translation efficiency. Read More

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http://dx.doi.org/10.3390/ijms19051347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983732PMC
May 2018
4 Reads

FSHD2- and BAMS-associated mutations confer opposing effects on SMCHD1 function.

J Biol Chem 2018 Jun 10;293(25):9841-9853. Epub 2018 May 10.

From the Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia,

Structural maintenance of chromosomes flexible hinge domain-containing 1 (Smchd1) plays important roles in epigenetic silencing and normal mammalian development. Recently, heterozygous mutations in have been reported in two disparate disorders: facioscapulohumeral muscular dystrophy type 2 (FSHD2) and Bosma arhinia microphthalmia syndrome (BAMS). FSHD2-associated mutations lead to loss of function; however, whether BAMS is associated with loss- or gain-of-function mutations in SMCHD1 is unclear. Read More

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http://dx.doi.org/10.1074/jbc.RA118.003104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016475PMC
June 2018
2 Reads

Small noncoding RNAs in FSHD2 muscle cells reveal both DUX4- and SMCHD1-specific signatures.

Hum Mol Genet 2018 May 8. Epub 2018 May 8.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by insufficient epigenetic repression of D4Z4 macrosatellite repeat where DUX4, an FSHD causing gene is embedded. There are two forms of FSHD, FSHD1 with contraction of D4Z4 repeat and FSHD2 with chromatin compaction defects mostly due to SMCHD1 mutation. Previous reports showed DUX4-induced gene expression changes as well as changes in microRNA expression in FSHD muscle cells. Read More

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http://dx.doi.org/10.1093/hmg/ddy173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048983PMC

Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle.

Hum Mol Genet 2018 Aug;27(R2):R153-R162

Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Facioscapulohumeral dystrophy (FSHD) is the third most prevalent muscular dystrophy. A progressive disease, it presents clinically as weakness and wasting of the face, shoulder and upper arm muscles, with later involvement of the trunk and lower extremities. FSHD develops through complex genetic and epigenetic events that converge on a common mechanism of toxicity with mis-expression of the transcription factor double homeobox 4 (DUX4). Read More

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http://dx.doi.org/10.1093/hmg/ddy162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061842PMC
August 2018
5 Reads

Lifetime endogenous estrogen exposure and disease severity in female patients with facioscapulohumeral muscular dystrophy.

Neuromuscul Disord 2018 Jun 8;28(6):508-511. Epub 2018 Mar 8.

Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by large variability in disease severity, that is only partly explained by (epi)genetic factors. Clinical observations and recent in vitro work suggest a protective effect of estrogens in FSHD. The aims of this study were to assess whether the lifetime endogenous estrogen exposure contributes to the variability in disease severity in female patients, and whether female patients experience changes in disease progression during periods of hormonal changes. Read More

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http://dx.doi.org/10.1016/j.nmd.2018.02.012DOI Listing
June 2018
3 Reads

Is Going Beyond Rasch Analysis Necessary to Assess the Construct Validity of a Motor Function Scale?

Arch Phys Med Rehabil 2018 Sep 3;99(9):1776-1782.e9. Epub 2018 Apr 3.

Université de Lyon, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS UMR 5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique Santé, Pierre-Bénite, France; L'Escale, Service de Médecine Physique et de Réadaptation Pédiatrique, Hôpital Femme-Mère-Enfant, Hospices Civils de Lyon, Bron, France. Electronic address:

Objective: To examine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.

Design: Observational cross-sectional multicenter study.

Setting: Twenty-three physical medicine departments, neurology departments, or reference centers for neuromuscular diseases. Read More

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http://dx.doi.org/10.1016/j.apmr.2018.02.017DOI Listing
September 2018
3 Reads

Functional domains of the FSHD-associated DUX4 protein.

Biol Open 2018 Apr 26;7(4). Epub 2018 Apr 26.

Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA

Aberrant expression of the full-length isoform of DUX4 (DUX4-FL) appears to underlie pathogenesis in facioscapulohumeral muscular dystrophy (FSHD). DUX4-FL is a transcription factor and ectopic expression of DUX4-FL is toxic to most cells. Previous studies showed that DUX4-FL-induced pathology requires intact homeodomains and that transcriptional activation required the C-terminal region. Read More

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http://dx.doi.org/10.1242/bio.033977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936065PMC
April 2018
6 Reads