1,403 results match your criteria Facioscapulohumeral Dystrophy


Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics.

Sci Rep 2020 Jul 9;10(1):11301. Epub 2020 Jul 9.

Department of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgique.

Intramuscular injection and electroporation of naked plasmid DNA (IMEP) has emerged as a potential alternative to viral vector injection for transgene expression into skeletal muscles. In this study, IMEP was used to express the DUX4 gene into mouse tibialis anterior muscle. DUX4 is normally expressed in germ cells and early embryo, and silenced in adult muscle cells where its pathological reactivation leads to Facioscapulohumeral muscular dystrophy. Read More

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http://dx.doi.org/10.1038/s41598-020-68135-7DOI Listing

Circulating Biomarkers in Muscular Dystrophies: Disease and Therapy Monitoring.

Mol Ther Methods Clin Dev 2020 Sep 22;18:230-239. Epub 2020 May 22.

Department of Molecular Genetics, Function & Therapy, The Cyprus Institute of Neurology and Genetics, PO Box 23462, 1683 Nicosia, Cyprus.

Muscular dystrophies are a group of inherited disorders that primarily affect the muscle tissues. Across the muscular dystrophies, symptoms commonly compromise the quality of life in all areas of functioning. It is well noted that muscular dystrophies need reliable and measurable biomarkers that will monitor the progress of the disease and evaluate the potential therapeutic approaches. Read More

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http://dx.doi.org/10.1016/j.omtm.2020.05.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327849PMC
September 2020

Evaluation of inflammatory lesions over 2 years in facioscapulohumeral muscular dystrophy.

Neurology 2020 Jul 1. Epub 2020 Jul 1.

Copenhagen Neuromuscular Center, section 3342, Department of Neurology, Rigshospitalet, Copenhagen University, Blegdamsvej 9, 2100 Copenhagen, Denmark.

Objective: We followed patients with facioscapulohumeral muscular dystrophy (FSHD) with sequential examinations over 2 years to investigate whether inflammatory lesions always precede fat replacement, if inflammation can be resolved without muscle degeneration, and if inflammatory lesions in muscle are always followed by fat replacement.

Methods: In this longitudinal study of 10 sequential MRI assessments over 2.5 years, we included 10 patients with FSHD. Read More

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http://dx.doi.org/10.1212/WNL.0000000000010155DOI Listing

Facioscapulohumeral muscular dystrophy (FSHD) and multiple sclerosis: a case report.

Acta Myol 2020 Mar 1;39(1):29-31. Epub 2020 Mar 1.

Department of Neurosciences, Odontostomatology and Reproductive Sciences, University "Federico II", Naples, Italy.

Facioscapulohumeral muscular dystrophy 1 (FSHD1) is an autosomal dominant neuromuscular disorder, associated with reduction of tandemly arrayed repetitive DNA elements D4Z4 (DRA), at 4q35. Few cases, especially carriers of 1-3 DRA show a syndromic form. Anecdotally the association of FSHD with multiple sclerosis (MS) is reported. Read More

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http://dx.doi.org/10.36185/2532-1900-005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315893PMC

Inhibition of expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy.

Proc Natl Acad Sci U S A 2020 Jun 29. Epub 2020 Jun 29.

Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada;

Facioscapulohumeral muscular dystrophy (FSHD), characterized by progressive muscle weakness and deterioration, is genetically linked to aberrant expression of in muscle. DUX4, in its full-length form, is cytotoxic in nongermline tissues. Here, we designed locked nucleic acid (LNA) gapmer antisense oligonucleotides (AOs) to knock down in immortalized FSHD myoblasts and the FSHD mouse model. Read More

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http://dx.doi.org/10.1073/pnas.1909649117DOI Listing

P38α Regulates Expression of DUX4 in Facioscapulohumeral Muscular Dystrophy.

J Pharmacol Exp Ther 2020 Jun 23. Epub 2020 Jun 23.

Fulcrum Therapeutics.

FSHD is caused by the loss of repression at the D4Z4 locus leading to DUX4 expression in skeletal muscle, activation of its early embryonic transcriptional program and muscle fiber death. While progress toward understanding the signals driving DUX4 expression has been made, the factors and pathways involved in the transcriptional activation of this gene remain largely unknown. Here, we describe the identification and characterization of p38α as a novel regulator of DUX4 expression in FSHD myotubes. Read More

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http://dx.doi.org/10.1124/jpet.119.264689DOI Listing

Mass spectrometry reveals the chemistry of formaldehyde cross-linking in structured proteins.

Nat Commun 2020 Jun 19;11(1):3128. Epub 2020 Jun 19.

Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, 9190401, Israel.

Whole-cell cross-linking coupled to mass spectrometry is one of the few tools that can probe protein-protein interactions in intact cells. A very attractive reagent for this purpose is formaldehyde, a small molecule which is known to rapidly penetrate into all cellular compartments and to preserve the protein structure. In light of these benefits, it is surprising that identification of formaldehyde cross-links by mass spectrometry has so far been unsuccessful. Read More

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http://dx.doi.org/10.1038/s41467-020-16935-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305180PMC

Deletion of the Williams Beuren syndrome critical region unmasks facioscapulohumeral muscular dystrophy.

Eur J Paediatr Neurol 2020 May 22. Epub 2020 May 22.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Department of of Molecular, Cell and Cancer Biology, University of Massachsetts Medical School, Worcester, USA. Electronic address:

Among 1339 unrelated cases accrued by the Italian National Registry for facioscapulohumeral muscular dystrophy (FSHD), we found three unrelated cases who presented signs of Williams-Beuren Syndrome (WBS) in early childhood and later developed FSHD. All three cases carry the molecular defects associated with the two disorders. The rarity of WBS and FSHD, 1 in 7500 and 1 in 20,000 respectively, makes a random association of the two diseases unlikely. Read More

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http://dx.doi.org/10.1016/j.ejpn.2020.05.006DOI Listing

Crystal structure of the hinge domain of Smchd1 reveals its dimerization mode and nucleic acid-binding residues.

Sci Signal 2020 Jun 16;13(636). Epub 2020 Jun 16.

Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia.

Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) is an epigenetic regulator in which polymorphisms cause the human developmental disorder, Bosma arhinia micropthalmia syndrome, and the degenerative disease, facioscapulohumeral muscular dystrophy. SMCHD1 is considered a noncanonical SMC family member because its hinge domain is C-terminal, because it homodimerizes rather than heterodimerizes, and because SMCHD1 contains a GHKL-type, rather than an ABC-type ATPase domain at its N terminus. The hinge domain has been previously implicated in chromatin association; however, the underlying mechanism involved and the basis for SMCHD1 homodimerization are unclear. Read More

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http://dx.doi.org/10.1126/scisignal.aaz5599DOI Listing

Herbal medicine significantly improved muscle function in a patient with type 1 facioscapulohumeral muscular dystrophy: A case report.

Explore (NY) 2020 May 24. Epub 2020 May 24.

The First Comprehensive Department, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Province Hospital of Chinese Medicine), Guangzhou, Guangdong, 510120, China. Electronic address:

Background And Aim: Facioscapulohumeral muscular dystrophy (FSHD) is a common muscular disorder. At present, treatments for FSHD have limited effects on the muscle function of patients. A famous Chinese medicine formula, Buzhong Yiqi (BZYQ), has shown promising effects on several muscular diseases, but evidence regarding its effect on FSHD is lacking. Read More

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http://dx.doi.org/10.1016/j.explore.2020.05.009DOI Listing

Anti-Müllerian hormone as an ovarian reserve marker in women with the most frequent muscular dystrophies.

Medicine (Baltimore) 2020 Jun;99(23):e20523

Department of Neurology, University Hospital Brno.

Some muscular dystrophies may have a negative impact on fertility. A decreased ovarian reserve is 1 of the factors assumed to be involved in fertility impairment. AMH (anti-Müllerian hormone) is currently considered the best measure of ovarian reserve. Read More

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http://dx.doi.org/10.1097/MD.0000000000020523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306369PMC

Homozygous nonsense variant in associated with facioscapulohumeral muscular dystrophy.

Neurology 2020 Jun 28;94(23):e2441-e2447. Epub 2020 May 28.

From the Department of Neuromuscular Research (K.H., S.M., M.O., S.N., I.N.), National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan; Department of Neurology (K.H.), Graduate School of Medicine, Kyoto University, Japan; Department of Human Genetics (D.Š., R.J.L.F.L., R.G., J.B., S.M.M.), Leiden University Medical Center, the Netherlands; Department of Clinical Development (S.M., I.N.), Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo; Department of Neurology (H.M., Y.S., A.S., K.S., S.K.), Graduate School of Medicine, Chiba University; Department of Biological Sciences (K.N., C.O.), Graduate School of Science, Osaka University; and Department of Pathophysiology (Y.K.H.), Tokyo Medical University, Tokyo, Japan.

Objective: Facioscapulohumeral muscular dystrophy (FSHD) is a heterogenetic disorder predominantly characterized by progressive facial and scapular muscle weakness. Patients with FSHD either have a contraction of the D4Z4 repeat on chromosome 4q35 or mutations in D4Z4 chromatin modifiers SMCHD1 and DNMT3B, both causing D4Z4 chromatin relaxation and inappropriate expression of the D4Z4-encoded gene in skeletal muscle. In this study, we tested the hypothesis whether , a known SMCHD1 protein interactor, is a disease gene for idiopathic FSHD2. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009617DOI Listing
June 2020
8.286 Impact Factor

Evolving genetic heterogeneity of facioscapulohumeral muscular dystrophy.

Neurology 2020 Jun 28;94(23):1011-1012. Epub 2020 May 28.

From the Department of Neurology (N.E.J.), Virginia Commonwealth University, Richmond; Department of Human Genetics (A.A.), Emory University School of Medicine, Atlanta, GA; and EGL Genetic Diagnostics LLC (A.A.), Tucker, GA.

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http://dx.doi.org/10.1212/WNL.0000000000009580DOI Listing

A novel shoulder disability staging system for scapulothoracic arthrodesis in patients with facioscapulohumeral dystrophy.

Orthop Traumatol Surg Res 2020 Jun 16;106(4):701-707. Epub 2020 May 16.

Koc University, School of Medicine, Department of Orthopaedics and Traumatology, Koc Universitesi Hastanesi, Davutpasa Cd. No:4 Topkapi-Zeytinburnu, 34010 Istanbul Turkey.

Background: Scapulothoracic arthrodesis (STA) is a well-established surgical technique to provide scapular stabilisation in patients with facioscapulohumeral dystrophy (FSHD). There is no staging or scoring systems available to guide surgical decision. The aim of this study was to develop a staging system to evaluate the shoulder disability in patients with FSHD to guide surgical decision-making and assess its reliability among surgeons. Read More

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http://dx.doi.org/10.1016/j.otsr.2020.03.002DOI Listing

Differential diagnosis of vacuolar myopathies in the NGS era.

Brain Pathol 2020 May 17. Epub 2020 May 17.

Institute of Neuropathology, RWTH Aachen University, Aachen, Germany.

Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non-inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late-onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar myopathy patients from 30 unrelated families, studied their clinical, histopathological and ultrastructural characteristics and performed genetic testing in index patients and relatives using Sanger sequencing and NGS including whole exome sequencing (WES). Read More

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http://dx.doi.org/10.1111/bpa.12864DOI Listing

[Clinical phenotype and genotype of early-onset facioscapulohumeral muscular dystrophy type 1].

Zhonghua Er Ke Za Zhi 2020 May;58(5):408-412

Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.

To explore the clinical, pathological and genetic characteristics of early-onset facioscapulohumeral muscular dystrophy type 1 (FSHD1), in order to increase awareness of the disease. In this retrospective study, the history of 3 patients, who were diagnosed with early-onset FSHD1 by molecular genetic test in Pediatric Outpatient Department of Peking University First Hospital from 4(th) June 2012 to 4(th) June 2018, were collected. Their clinical data, genotypes, phenotypes and pathological features of muscle biopsy were analyzed. Read More

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http://dx.doi.org/10.3760/cma.j.cn112140-20191015-00648DOI Listing

Phenotypic Variability Among Patients With D4Z4 Reduced Allele Facioscapulohumeral Muscular Dystrophy.

JAMA Netw Open 2020 May 1;3(5):e204040. Epub 2020 May 1.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Importance: Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disorder, associated with the deletion of tandemly arrayed D4Z4 repetitive elements. The extensive use of molecular analysis of the D4Z4 locus for FSHD diagnosis has revealed wide clinical variability, suggesting that subgroups of patients exist among carriers of the D4Z4 reduced allele (DRA).

Objective: To investigate the clinical expression of FSHD in the genetic subgroup of carriers of a DRA with 7 to 8 repeat units (RUs). Read More

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http://dx.doi.org/10.1001/jamanetworkopen.2020.4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195625PMC

Facioscapulohumeral Muscular Dystrophy-a Tale of Heterogeneity and the Power of Clinical Assessments.

JAMA Netw Open 2020 May 1;3(5):e205004. Epub 2020 May 1.

Aix Marseille University, Marseille Medical Genetics MMG, Marseille, France.

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http://dx.doi.org/10.1001/jamanetworkopen.2020.5004DOI Listing

A quantitative method to assess muscle edema using short TI inversion recovery MRI.

Sci Rep 2020 Apr 29;10(1):7246. Epub 2020 Apr 29.

Copenhagen Neuromuscular Center, Section 3342, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Muscle inflammation is an important component of disease pathophysiology in several muscular dystrophies. Hyperintensities on MRI sequences with short TI inversion recovery (STIR) reflect edema, or inflammation (STIR+). Conventionally, STIR evaluation has been done by visual inspection. Read More

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http://dx.doi.org/10.1038/s41598-020-64287-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190715PMC

PAX7 target gene repression associates with FSHD progression and pathology over one year.

Hum Mol Genet 2020 Apr 29. Epub 2020 Apr 29.

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, inherited skeletal myopathy linked to hypomethylation of the D4Z4 macrosatellite at chromosome 4q35. This epigenetic de-repression permits expression of the transcription factor DUX4, which may drive pathology by direct activation of target genes, or through inhibition of the homologous transcription factor PAX7. We demonstrated that PAX7 target gene repression is a superior biomarker of FSHD status, compared to DUX4 target gene expression. Read More

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http://dx.doi.org/10.1093/hmg/ddaa079DOI Listing

103 Atypical Progressive Bulbar Palsy presenting with Dropped Head.

CNS Spectr 2020 Apr;25(2):267

Associate Professor, Neurology Department, Loyola University Medical Center, Chicago, USA.

Introduction: Typical amyotrophic lateral sclerosis (ALS) presents on neurological examination with specific signs of upper and lower motor neuron degeneration (Brooks et al, 1995), which can account for 85% of patients with ALS (Turner and Talbot, 2013). There are different types of clinical presentations, including progressive bulbar palsy (PBP), Limb-onset ALS, progressive muscular atrophy (PMA) and upper motor neuron (UMN) predominant ALS. PBP has mainly brainstem signs. Read More

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http://dx.doi.org/10.1017/S1092852920000218DOI Listing
April 2020
2.710 Impact Factor

Facioscapulohumeral muscular dystrophy 1 patients participating in the UK FSHD registry can be subdivided into 4 patterns of self-reported symptoms.

Neuromuscul Disord 2020 Apr 12;30(4):315-328. Epub 2020 Mar 12.

John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Centre for Life, Newcastle NE1 3BZ, UK.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant incurable skeletal muscle disease. FSHD1 constitutes 95% of cases and is linked to truncation of the D4Z4 macrosatellite at 4q35. In most cases the condition initially presents with facial and proximal weakness of the upper limbs, but over the course of the disease involves lower limb and truncal muscles. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.03.001DOI Listing

Outcomes of scapulothoracic fusion in facioscapulohumeral muscular dystrophy: A systematic review.

Shoulder Elbow 2020 Apr 14;12(2):75-90. Epub 2019 Aug 14.

Division of Orthopaedic Surgery, Department of Surgery, McMaster University, Hamilton, Canada.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition associated with selective weakness of the muscles of the upper arm, face, and shoulder girdle, negatively affecting daily activities. Scapulothoracic arthrodesis may restore shoulder function and improve quality of life. The purpose of this review is to evaluate the outcomes and complications of scapulothoracic arthrodesis in FSHD patients. Read More

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http://dx.doi.org/10.1177/1758573219866195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153204PMC

Non-Union After Multiple Lumbar Fusion Surgeries in a Patient With Facioscapulohumeral Muscular Dystrophy: A Case Report and Review of the Literature.

World Neurosurg 2020 Apr 18;139:281-285. Epub 2020 Apr 18.

Department of Neurosurgery, Penn State Health, Hershey, Pennsylvania, USA.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a rare condition affecting 1/20,000 persons and the third most common muscular dystrophy condition, with an autosomal dominant pattern of inheritance characterized by progressive muscular weakness primarily involving the face, shoulder girdle, and upper arm. The condition is associated with atrophic musculature of the trunk and core leading to difficulties with gait, posture, and function. FSHD leaves as many as 20% of patients wheelchair-bound and most commonly presents with low back, neck, and shoulder pain. Read More

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http://dx.doi.org/10.1016/j.wneu.2020.04.030DOI Listing

Interpretation of the Epigenetic Signature of Facioscapulohumeral Muscular Dystrophy in Light of Genotype-Phenotype Studies.

Int J Mol Sci 2020 Apr 10;21(7). Epub 2020 Apr 10.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by incomplete penetrance and intra-familial clinical variability. The disease has been associated with the genetic and epigenetic features of the D4Z4 repetitive elements at 4q35. Recently, D4Z4 hypomethylation has been proposed as a reliable marker in the FSHD diagnosis. Read More

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http://dx.doi.org/10.3390/ijms21072635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178248PMC
April 2020
2.862 Impact Factor

Transgenic mice expressing tunable levels of DUX4 develop characteristic facioscapulohumeral muscular dystrophy-like pathophysiology ranging in severity.

Skelet Muscle 2020 Apr 11;10(1). Epub 2020 Apr 11.

Department of Pharmacology, School of Medicine, University of Nevada, Reno, Reno, NV, 89557, USA.

Background: All types of facioscapulohumeral muscular dystrophy (FSHD) are caused by the aberrant activation of the somatically silent DUX4 gene, the expression of which initiates a cascade of cellular events ultimately leading to FSHD pathophysiology. Typically, progressive skeletal muscle weakness becomes noticeable in the second or third decade of life, yet there are many individuals who are genetically FSHD but develop symptoms much later in life or remain relatively asymptomatic throughout their lives. Conversely, FSHD may clinically present prior to 5-10 years of age, ultimately manifesting as a severe early-onset form of the disease. Read More

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http://dx.doi.org/10.1186/s13395-020-00227-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149937PMC

It's not all about muscle: fibroadipogenic progenitors contribute to facioscapulohumeral muscular dystrophy.

J Clin Invest 2020 May;130(5):2186-2188

Center for Genetic Muscle Disorders, Kennedy Krieger Institute, Baltimore, Maryland, USA.

Facioscapulohumeral muscular dystrophy (FSHD) results from expression of the full-length double homeobox 4 (DUX4-FL) retrogene in skeletal muscle. However, even in cases of severe FSHD the presence of DUX4 is barely detectable. In this issue of the JCI, Bosnakovski et al. Read More

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http://dx.doi.org/10.1172/JCI136133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190910PMC

Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice.

J Clin Invest 2020 May;130(5):2465-2477

Lillehei Heart Institute and.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by loss of repression of the DUX4 gene; however, the DUX4 protein is rare and difficult to detect in human muscle biopsies, and pathological mechanisms are obscure. FSHD is also a chronic disease that progresses slowly over decades. We used the sporadic, low-level, muscle-specific expression of DUX4 enabled by the iDUX4pA-HSA mouse to develop a chronic long-term muscle disease model. Read More

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http://dx.doi.org/10.1172/JCI133303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190912PMC
May 2020
13.215 Impact Factor

DUX4-expressing immortalised FSHD lymphoblastoid cells express genes elevated in FSHD muscle biopsies, correlating with the early stages of inflammation.

Hum Mol Genet 2020 Apr 2. Epub 2020 Apr 2.

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 an incurable disorder linked to ectopic expression of DUX4. However, DUX4 is notoriously difficult to detect in FSHD muscle cells, while DUX4 target gene expression is an inconsistent biomarker for FSHD skeletal muscle biopsies, displaying efficacy only on pathologically inflamed samples. Immune gene misregulation occurs in FSHD muscle, with DUX4 target genes enriched for those associated with inflammatory processes. Read More

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http://dx.doi.org/10.1093/hmg/ddaa053DOI Listing

Applying genome-wide CRISPR-Cas9 screens for therapeutic discovery in facioscapulohumeral muscular dystrophy.

Sci Transl Med 2020 Mar;12(536)

Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA 02115, USA.

The emergence of CRISPR-Cas9 gene-editing technologies and genome-wide CRISPR-Cas9 libraries enables efficient unbiased genetic screening that can accelerate the process of therapeutic discovery for genetic disorders. Here, we demonstrate the utility of a genome-wide CRISPR-Cas9 loss-of-function library to identify therapeutic targets for facioscapulohumeral muscular dystrophy (FSHD), a genetically complex type of muscular dystrophy for which there is currently no treatment. In FSHD, both genetic and epigenetic changes lead to misexpression of , the FSHD causal gene that encodes the highly cytotoxic DUX4 protein. Read More

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http://dx.doi.org/10.1126/scitranslmed.aay0271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304480PMC

Type 1 FSHD with 6-10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention.

Int J Mol Sci 2020 Mar 23;21(6). Epub 2020 Mar 23.

Reference Center of Neuromuscular disorders and ALS, Timone University Hospital, AP-HM, 264 rue Saint-Pierre, Cedex 05 13385 Marseille, France.

Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study compared (1) the phenotype and severity of FSHD1 between patients carrying 6-8 vs. 9-10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). Read More

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http://dx.doi.org/10.3390/ijms21062221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139460PMC

G-quadruplex ligands mediate downregulation of DUX4 expression.

Nucleic Acids Res 2020 05;48(8):4179-4194

Department of Biological Sciences, Royal Holloway-University of London, Egham, Surrey TW20 0EX, UK.

Abnormal DUX4 expression in skeletal muscles plays a key role in facioscapulohumeral muscular dystrophy (FSHD) pathogenesis, although the molecular mechanisms regulating DUX4 expression are not fully defined. Using bioinformatic analysis of the genomic DUX4 locus, we have identified a number of putative G-quadruplexes (GQs) forming sequences. Their presence was confirmed in synthetic oligonucleotiode sequences derived from the enhancer, promoter and transcript of DUX4 through circular dichroism and nuclear magnetic resonance analysis. Read More

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http://dx.doi.org/10.1093/nar/gkaa146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192601PMC

Clinical and genetic features of somatic mosaicism in facioscapulohumeral dystrophy.

J Med Genet 2020 Mar 13. Epub 2020 Mar 13.

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

Purpose: To analyse the clinical spectrum, genetic features, specific D4Z4 hypomethylation status and genotype-phenotype correlations for somatic mosaicism in facioscapulohumeral dystrophy (FSHD).

Methods: This was a prospective, hospital-based, case-control, observational study of 35 participants with FSHD with somatic mosaicism recruited over 10 years, with 17 penetrant patients and 18 non-penetrant mutation carriers. This study also included a univariate comparison of 17 paired mosaic and non-mosaic patients with FSHD. Read More

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http://dx.doi.org/10.1136/jmedgenet-2019-106638DOI Listing

A hospital based epidemiological study of genetically determined muscle disease in south western Norway.

Neuromuscul Disord 2020 03 4;30(3):181-185. Epub 2020 Feb 4.

Department of Clinical Medicine, University of Bergen, Norway; Department of Neurology, Haukeland University Hospital, Bergen, Norway. Electronic address:

We determined the prevalence of genetically determined neuromuscular diseases in adult Norwegian patients from Hordaland County. We identified patients using International Classification of Disease codes registered in our hospital database and reviewed patient notes to ensure diagnostic accuracy. To ensure maximal ascertainment, we screened both inpatient and outpatient contacts from two 5-year periods 01. Read More

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http://dx.doi.org/10.1016/j.nmd.2020.01.006DOI Listing

Muscle ultrasound is a responsive biomarker in facioscapulohumeral dystrophy.

Neurology 2020 Apr 4;94(14):e1488-e1494. Epub 2020 Mar 4.

From the Department of Neurology, Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands.

Objective: With drug trials starting soon, responsive, relevant, and patient-friendly biomarkers are highly needed in facioscapulohumeral dystrophy (FSHD). Our objective was to assess muscle ultrasound (MUS) as an imaging biomarker in patients with FSHD.

Methods: One-year observational, longitudinal study of both quantitative and qualitative MUS changes in FSHD. Read More

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http://dx.doi.org/10.1212/WNL.0000000000009211DOI Listing

Does DNA Methylation Matter in FSHD?

Genes (Basel) 2020 02 28;11(3). Epub 2020 Feb 28.

Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 4,41121 Modena, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) has been associated with the genetic and epigenetic molecular features of the CpG-rich D4Z4 repeat tandem array at 4q35. Reduced DNA methylation of D4Z4 repeats is considered part of the FSHD mechanism and has been proposed as a reliable marker in the FSHD diagnostic procedure. We considered the assessment of D4Z4 DNA methylation status conducted on distinct cohorts using different methodologies. Read More

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http://dx.doi.org/10.3390/genes11030258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140823PMC
February 2020

Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy.

Clin Genet 2020 Jun 4;97(6):799-814. Epub 2020 Mar 4.

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

Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. Read More

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http://dx.doi.org/10.1111/cge.13726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318180PMC

Longitudinal measures of RNA expression and disease activity in FSHD muscle biopsies.

Hum Mol Genet 2020 Apr;29(6):1030-1043

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

Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to the discovery of candidate therapeutics, and it is important to identify markers of disease activity to inform clinical trial design. For drugs that inhibit DUX4 expression, measuring DUX4 or DUX4-target gene expression might be an interim measure of drug activity; however, only a subset of FHSD muscle biopsies shows evidence of DUX4 expression. Our prior study showed that MRI T2-STIR-positive muscles had a higher probability of showing DUX4 expression than muscles with normal MRI characteristics. Read More

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http://dx.doi.org/10.1093/hmg/ddaa031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158378PMC

SMCHD1 promotes ATM-dependent DNA damage signaling and repair of uncapped telomeres.

EMBO J 2020 Apr 21;39(7):e102668. Epub 2020 Feb 21.

Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.

Structural maintenance of chromosomes flexible hinge domain-containing protein 1 (SMCHD1) has been implicated in X-chromosome inactivation, imprinting, and DNA damage repair, and mutations in SMCHD1 can cause facioscapulohumeral muscular dystrophy. More recently, SMCHD1 has also been identified as a component of telomeric chromatin. Here, we report that SMCHD1 is required for DNA damage signaling and non-homologous end joining (NHEJ) at unprotected telomeres. Read More

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http://dx.doi.org/10.15252/embj.2019102668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110143PMC

Spinal fusion in facioscapulohumeral dystrophy for hyperlordosis: A case report.

Medicine (Baltimore) 2020 Feb;99(8):e18787

Koc University, School of Medicine, Department of Orthopaedics and Traumatology.

Rationale: Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy, which is associated with facial, shoulder girdle, and paraspinal muscle atrophy. Most of the patients develop hypokyphosis and hyperlordosis in the course of the disease, to preserve standing posture. Corrective fusion is contraindicated in these patients as the surgery results with loss of compensatory hyperlordosis and leads to loss of trunk balance while standing. Read More

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http://dx.doi.org/10.1097/MD.0000000000018787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034682PMC
February 2020

Electrical impedance myography: MRI-like data without the need for MRI.

Authors:
Seward B Rutkove

Muscle Nerve 2020 05 20;61(5):554-556. Epub 2020 Feb 20.

Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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http://dx.doi.org/10.1002/mus.26832DOI Listing

[Analysis of D4Z4 mutation in a child with facioscapulohumeral muscular dystrophy presented initially as mental retardation].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Feb;37(2):150-152

Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510000, China.

Objective: To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation.

Methods: Wechsler Intelligence Scale for Children Revised in China (WISC-IV) was used to assess the patient's IQ. Other clinical data was also collected. Read More

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http://dx.doi.org/10.3760/cma.j.issn.1003-9406.2020.02.012DOI Listing
February 2020

Reply to J. Dulski and J. Slawek's "Fibrodysplasia ossificans progressiva as a form of pseudodystonia".

Parkinsonism Relat Disord 2020 02 28;71:49-50. Epub 2020 Jan 28.

Department of Neurology, University Medical Centre Ljubljana, Zaloška 2, 1000 Ljubljana, Slovenia. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2020.01.016DOI Listing
February 2020

Updating the Clinical Picture of Facioscapulohumeral Muscular Dystrophy: Ramifications for Drug Development With Potential Solutions.

Ther Innov Regul Sci 2020 01 6;54(1):144-150. Epub 2020 Jan 6.

North Carolina State University's College of Veterinary Medicine, Raleigh, North Carolina, USA.

Background: Facioscapulohumeral muscular dystrophy (FSHD) is a complex, inheritable, and rare muscle disease that affects the entire body. The major symptom of FSHD is progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo), and upper arms (humeral). Read More

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http://dx.doi.org/10.1007/s43441-019-00038-wDOI Listing
January 2020

Myopathies presenting with head drop: Clinical spectrum and treatment outcomes.

Neuromuscul Disord 2020 02 12;30(2):128-136. Epub 2019 Dec 12.

Department of Neurology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Dropped head syndrome can be the presenting feature of a wide spectrum of neurological conditions. In this study, we aimed to define the clinical characteristics and treatment outcomes of 107 patients, where head drop was the presenting or predominant clinical feature of a myopathy. Median age at presentation was 68 years (range 42-88). Read More

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http://dx.doi.org/10.1016/j.nmd.2019.12.001DOI Listing
February 2020

Bilateral scapulothoracic arthrodesis for facioscapulohumeral muscular dystrophy: function, fusion, and respiratory consequences.

J Shoulder Elbow Surg 2020 May 22;29(5):931-940. Epub 2020 Jan 22.

Department of Orthopaedics, University Institute for Locomotion and Sports, Pasteur 2 Hospital, Nice, France.

Background: Scapulothoracic arthrodesis (STA) has been proposed for the treatment of painful scapular winging in patients with facioscapulohumeral muscular dystrophy (FSHD). However, the rate of osseous fusion is variable, and there is a theoretical risk of reduced respiratory function after bilateral STA.

Methods: This was a retrospective study of 10 STAs, performed sequentially, in 5 FSHD patients. Read More

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http://dx.doi.org/10.1016/j.jse.2019.10.006DOI Listing

DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy.

Int J Mol Sci 2020 Jan 22;21(3). Epub 2020 Jan 22.

Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G2H7, Canada.

Facioscapulohumeral muscular dystrophy (FSHD) is a disabling inherited muscular disorder characterized by asymmetric, progressive muscle weakness and degeneration. Patients display widely variable disease onset and severity, and sometimes present with extra-muscular symptoms. There is a consensus that FSHD is caused by the aberrant production of the double homeobox protein 4 (DUX4) transcription factor in skeletal muscle. Read More

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http://dx.doi.org/10.3390/ijms21030729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037115PMC
January 2020

Preserved single muscle fiber specific force in facioscapulohumeral muscular dystrophy.

Neurology 2020 03 21;94(11):e1157-e1170. Epub 2020 Jan 21.

From the Department of Neurology, Donders Institute for Brain, Cognition and Behaviour (S.L., N.C.V., B.G.M.v.E.), Department of Radiology (A.H.), and Department of Pulmonary Diseases (H.V.H.), Radboud University Medical Center, Nijmegen; Department of Physiology (S.L., R.v.d.P., M.v.d.B., C.A.C.O.) and Department of Pathology, Institute for Cardiovascular Research (B.K.), Amsterdam University Medical Center, the Netherlands; Department of Cellular and Molecular Medicine (R.v.d.P., C.A.C.O.), University of Arizona, Tucson; and Department of Human Genetics (S.M.v.d.M.), Leiden University Medical Centre, the Netherlands.

Objective: To investigate single muscle fiber contractile performance in muscle biopsies from patients with facioscapulohumeral muscular dystrophy (FSHD), one of the most common hereditary muscle disorders.

Methods: We collected 50 muscle biopsies (26 vastus lateralis, 24 tibialis anterior) from 14 patients with genetically confirmed FSHD and 12 healthy controls. Single muscle fibers (n = 547) were isolated for contractile measurements. Read More

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http://dx.doi.org/10.1212/WNL.0000000000008977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220237PMC