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JCI Insight 2019 Apr 16;5. Epub 2019 Apr 16.

Nemaline myopathy is a congenital neuromuscular disorder characterized by muscle weakness, fiber atrophy and presence of nemaline bodies within myofibers. However, the understanding of underlying pathomechanisms is lacking. Recently, mutations in KBTBD13, KLHL40 and KLHL41, three substrate adaptors for the E3-ubiquitin ligase Cullin-3, have been associated with early-onset nemaline myopathies. Read More

Neuromuscul Disord 2019 Mar 2. Epub 2019 Mar 2.

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. Electronic address:

Actinopathy is a group of clinically and pathologically heterogeneous myopathies due to mutations in the skeletal muscle sarcomeric α-actin 1-encoding gene (ACTA1). Disease-onset spans from prenatal life to adulthood and weakness can preferentially affect proximal or distal muscles. Myopathological findings include a spectrum of structural abnormalities with nemaline rods being the most common. Read More

Mitochondrion 2019 Apr 12. Epub 2019 Apr 12.

Medical Genetics-Neurogenetics, IRCCS Foundation, C. Besta Neurological Institute, Milan, Italy. Electronic address:

Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders presenting at birth with psychomotor delay, cognitive impairment, muscle weakness and hypotonia. Here we described an alteration of mitochondrial inner membrane potential and mitochondrial network in cells derived from Italian patients carrying three novel mutations in CHKB gene, recently associated with "megaconial CMD". On the bases of our findings, we hypothesize that the mitochondrial membrane potential alteration, presumably as a consequence of the altered biosynthesis of phosphatidylcholine, could be responsible for the peculiar morphological aspect of mitochondria in this disease and might be involved in the disease pathogenesis. Read More

Clin Investig Arterioscler 2019 Apr 9. Epub 2019 Apr 9.

Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, La Rioja, España.

Statins are contraindicated in patients with myopathies. Until a few years ago, in those patients with Familial Hypercholesterolemia who also presented muscular dystrophies and didńt reach adequate cholesterol plasmatic levels, the next therapeutic ladder was lipoapheresis. When iPCSK9 first appeared, lipoapheresis could be suspended in some of these patients, sustaining nevertheless proper levels of cholesterol. Read More

Am J Phys Med Rehabil 2019 Apr 9. Epub 2019 Apr 9.

Rehabilitation Research Center at Santa Clara Valley Medical Center, San Jose, CA.

Mechanical insufflation-exsufflation (MIE), or "cough-assist" is a commonly used method of clearing tracheal and pulmonary secretions in patients with respiratory insufficiency secondary to spinal cord injury (SCI). This report presents a novel technique termed the Pharyngeal Clearance Maneuver (PCM) which utilizes a modified application of the MIE device to mobilize "secretion burden" at the portion of the trachea above the tracheostomy cuff during cuff deflation. Utilization of this strategy may reduce the risk of aspiration, infection, and respiratory compromise for patients with high cervical SCI in the acute rehabilitation setting. Read More

Eur J Anaesthesiol 2019 Apr 3. Epub 2019 Apr 3.

From the Department of Anaesthesiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark (EL-M, ML-K, JB-S, CM-S, MV-M, MR-G).

Background: Nondepolarising muscle relaxants (NDMRs) provide optimal conditions for tracheal intubation and improve surgical conditions. Several clinical conditions, diseases and pharmacological interactions have been suggested to cause resistance towards NDMRs that may translate into difficult intubation or inadequate operating conditions during surgery.

Objective: The aim of this study was to evaluate the current evidence of patient groups with resistance towards NDMRs. Read More

Hum Mutat 2019 Apr 1. Epub 2019 Apr 1.

Department of Biomedicine, Basel University Hospital, Basel, Switzerland.

Congenital myopathies are early onset, slowly progressive neuromuscular disorders of variable severity. They are genetically and phenotypically heterogeneous and caused by pathogenic variants in several genes. Multi-minicore Disease, one of the more common congenital myopathies, is frequently caused by recessive variants in either SELENON, encoding the endoplasmic reticulum glycoprotein selenoprotein N or RYR1, encoding a protein involved in calcium homeostasis and excitation-contraction coupling. Read More

Emerg Top Life Sci 2019 Mar 28;3(1):19-37. Epub 2019 Jan 28.

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.

Despite recent scientific advances, most rare genetic diseases - including most neuro-muscular diseases - do not currently have curative gene-based therapies available. However, in some cases, such as vitamin, cofactor or enzyme deficiencies, channelopathies and disorders of the neuromuscular junction, a confirmed genetic diagnosis provides guidance on treatment, with drugs available that may significantly alter the disease course, improve functional ability and extend life expectancy. Nevertheless, many treatable patients remain undiagnosed or do not receive treatment even after genetic diagnosis. Read More

Mol Ther Nucleic Acids 2019 Feb 27;16:246-256. Epub 2019 Feb 27.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch 67404, France; INSERM U1258, Illkirch 67404, France; CNRS UMR7104, Illkirch 67404, France; Strasbourg University, Illkirch 67404, France. Electronic address:

Genome editing with the CRISPR/Cas9 technology has emerged recently as a potential strategy for therapy in genetic diseases. For dominant mutations linked to gain-of-function effects, allele-specific correction may be the most suitable approach. In this study, we tested allele-specific inactivation or correction of a heterozygous mutation in the Dynamin 2 (DNM2) gene that causes the autosomal dominant form of centronuclear myopathies (CNMs), a rare muscle disorder belonging to the large group of congenital myopathies. Read More

Redox Biol 2019 Mar 23;24:101176. Epub 2019 Mar 23.

Dulbecco Telethon Institute at Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy. Electronic address:

Selenoprotein N (SELENON) is an endoplasmic reticulum (ER) protein whose loss of function leads to a congenital myopathy associated with insulin resistance (SEPN1-related myopathy). The exact cause of the insulin resistance in patients with SELENON loss of function is not known. Skeletal muscle is the main contributor to insulin-mediated glucose uptake, and a defect in this muscle-related mechanism triggers insulin resistance and glucose intolerance. Read More

Genet Test Mol Biomarkers 2019 Mar 22. Epub 2019 Mar 22.

1 Department of Pathology, Princess Margaret Hospital, Hong Kong, China.

Aims: Muscle disorders are clinically and genetically heterogeneous. Investigations, including plasma creatine kinase, electromyography, and nerve conduction velocity studies, might be nonspecific, whereas muscle biopsy might be limited by sampling bias and variable histopathology. Next-generation sequencing is now generally considered an important diagnostic tool for muscle disorders, with decreased costs and improved diagnostic yield. Read More

Mol Genet Genomic Med 2019 Mar 18:e621. Epub 2019 Mar 18.

Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.

Background: X-linked myotubular myopathy (XLMTM) is a form of the severest congenital muscle diseases characterized by marked muscle weakness, hypotonia, and feeding and breathing difficulties in male infants. It is caused by mutations in the myotubularin gene (MTM1).

Methods: Evaluation of clinical history and examination of muscle pathology of three patients and comprehensive genome analysis on our original targeted gene panel system for muscular diseases. Read More

J Neurol 2019 Mar 14. Epub 2019 Mar 14.

Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: To evaluate the prevalence of cardiac involvement in patients with congenital myopathies and the association to specific genotypes.

Methods: We evaluated patients with physical examination, electrocardiogram, echocardiography, and 48-h Holter monitoring. Follow-up was performed for major events. Read More

Neuromuscul Disord 2019 Apr 7;29(4):330-340. Epub 2019 Feb 7.

Spierziekten Nederland, Baarn, The Netherlands.

Since 1992, the European Neuromuscular Centre facilitated workshops to bring experts in the field of neuromuscular disorders together. After organising more than 235 workshops, it is time to evaluate what impact these 25 years of ENMC workshops have had on the neuromuscular research field and on people affected by a neuromuscular condition. To measure this, workshop topics were retrospectively evaluated and bibliometric analyses on the citation scores of ENMC-derived publications were performed. Read More

Hum Mutat 2019 Feb 28. Epub 2019 Feb 28.

Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-CDG (formerly CDG-IIm). To date, twenty-nine unique de novo variants from thirty-two unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Read More

Sci Rep 2019 Feb 26;9(1):2770. Epub 2019 Feb 26.

School of Biological Sciences, University of Reading, Reading, UK.

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. Read More

BMC Neurol 2019 Feb 26;19(1):32. Epub 2019 Feb 26.

Department of Neurology, Affiliated Qianfoshan Hospital of Shandong University, NO.16766, Jingshi Road, Shandong, Jinan, 250014, CN, China.

Background: Collagen VI-related myopathies are a spectrum of muscular diseases with features of muscle weakness and atrophy, multiple contractures of joints, distal hyperextensibility, severe respiratory dysfunction and cutaneous alterations, attributable to mutations in the COL6A1, COL6A2, and COL6A3 genes. However, no case of collagen VI mutations with hematuria has been reported. We report a 14-year-old boy who had both Bethlem myopathy and recurrent hematuria and who carried a known de novo COL6A1 missense mutation c. Read More

Gene 2019 May 19;697:159-164. Epub 2019 Feb 19.

Medical Genetics Laboratory, Petrovsky Russian Research Center of Surgery, Moscow 119991, Russia; Pirogov Russian National Research Medical University, Moscow 117997, Russia.

Mutations in the MYH7 gene are the source of an allelic series of diseases, including various cardiomyopathies and skeletal myopathies that usually manifest in adulthood. We observed a 1.5 y. Read More

Skelet Muscle 2019 Feb 21;9(1). Epub 2019 Feb 21.

Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1020, New York, NY, 10029, USA.

Background: Group I Paks are serine/threonine kinases that function as major effectors of the small GTPases Rac1 and Cdc42, and they regulate cytoskeletal dynamics, cell polarity, and transcription. We previously demonstrated that Pak1 and Pak2 function redundantly to promote skeletal myoblast differentiation during postnatal development and regeneration in mice. However, the roles of Pak1 and Pak2 in adult muscle homeostasis are unknown. Read More

J Neurol 2019 Apr 20;266(4):876-887. Epub 2019 Feb 20.

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

Objective: The histopathological features of malignant hyperthermia (MH) and non-anaesthetic (mostly exertional) rhabdomyolysis (RM) due to RYR1 mutations have only been reported in a few cases.

Methods: We performed a retrospective multi-centre cohort study focussing on the histopathological features of patients with MH or RM due to RYR1 mutations (1987-2017). All muscle biopsies were reviewed by a neuromuscular pathologist. Read More

Nat Commun 2019 02 15;10(1):797. Epub 2019 Feb 15.

Instituto de Investigaciones Biomédicas "Alberto Sols", CSIC-UAM, 28029, Madrid, Spain.

FXR1 is an alternatively spliced gene that encodes RNA binding proteins (FXR1P) involved in muscle development. In contrast to other tissues, cardiac and skeletal muscle express two FXR1P isoforms that incorporate an additional exon-15. We report that recessive mutations in this particular exon of FXR1 cause congenital multi-minicore myopathy in humans and mice. Read More

J Neuropathol Exp Neurol 2019 Feb 4. Epub 2019 Feb 4.

Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.

The phenotypes associated with pathogenic variants in the ryanodine receptor 1 gene (RYR1, OMIM# 180901) have greatly expanded over the last few decades as genetic testing for RYR1 variants has become more common. Initially described in association with malignant hyperthermia, pathogenic variants in RYR1 are typically associated with core pathology in muscle biopsies (central core disease or multiminicore disease) and symptomatic myopathies with symptoms ranging from mild weakness to perinatal lethality. We describe a 2-week-old male patient with multiple congenital dysmorphisms, severe perinatal weakness, and subsequent demise, whose histopathology on autopsy was consistent with congenital muscular dystrophy. Read More

Acta Neuropathol 2019 Mar 30;137(3):501-519. Epub 2019 Jan 30.

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1, rue Laurent Fries, BP 10142, 67404, Illkirch, France.

The identification of genes implicated in myopathies is essential for diagnosis and for revealing novel therapeutic targets. Here we characterize a novel subclass of congenital myopathy at the morphological, molecular, and functional level. Through exome sequencing, we identified de novo ACTN2 mutations, a missense and a deletion, in two unrelated patients presenting with progressive early-onset muscle weakness and respiratory involvement. Read More

Zhonghua Er Ke Za Zhi 2019 Feb;57(2):142-145

Department of Pediatrics, Xiangya Hospital of Central South University; Hunan Intellectual and Developmental Disabilities Research Center, Changsha 410008, China.

To summarize the clinical manifestations and gene variations of combined immunodeficiency caused by ORAI1 variation with a case report and literature review. The clinical data of the patient who was diagnosed with ORAI1 variation caused combined immunodeficiency in the Department of Pediatrics in Xiangya Hospital of Central South University in February 2018 were extracted and analyzed. The literature till August 2018 was searched with key words of 'ORAI1', and 'immunodeficiency' in both English and Chinese in the database of China national knowledge infrast ructure (CNKI), Wanfang and Pubmed. Read More

Zhonghua Er Ke Za Zhi 2019 Feb;57(2):136-141

Department of Neurology, Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.

To summarize the clinical manifestations and determine the molecular etiology for two collagen type Ⅵ-related myopathy pedigrees. Two spontaneous collagen type Ⅵ-related myopathy patients were admitted to Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in October 2017. Clinical data of probands and their family members were collected and their genomic DNA was obtained for genetic testing. Read More

J Am Soc Echocardiogr 2019 Mar 21;32(3):412-422. Epub 2019 Jan 21.

PHYMEDEXP, University of Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.

Background: Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Speckle-tracking echocardiographic (STE) imaging is emerging as a noninvasive functional biomarker to consider in the early detection of DMD-related cardiomyopathy. However, STE analysis has not been assessed in a prospectively controlled study, especially in presymptomatic children with DMD, and no study has used STE analysis in all three displacements (longitudinal, radial, and circumferential) and for both ventricles. Read More

Neurology 2019 Feb 23;92(8):e866-e878. Epub 2019 Jan 23.

From The Heart Institute (M.T., J.J., B.G.), Cincinnati Children's Hospital Medical Center, OH; Department of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center (B.B.), and Division of Pediatric Cardiology, Congenital Heart Center (J.F.), University of Florida, Gainesville; Department of Cardiology (J.L., B.A.-V., M.R.O.), Johns Hopkins University, Baltimore, MD; Smidt Heart Institute (R.M., E.M., R.G.V.), Cedars-Sinai Medical Center, Los Angeles, CA; Capricor Therapeutics (R.R.S., B.F., J.R., J.M.P., L.M., D.D.A.), Beverly Hills, CA; and Department of Cardiology (K.M.), Laikon Hospital, Athens, Greece.

Objective: To assess the feasibility, safety, and efficacy of intracoronary allogeneic cardiosphere-derived cells (CAP-1002) in patients with Duchenne muscular dystrophy (DMD).

Methods: The Halt Cardiomyopathy Progression (HOPE)-Duchenne trial is a phase I/II, randomized, controlled, open-label trial (NCT02485938). Patients with DMD >12 years old, with substantial myocardial fibrosis, were randomized (1:1) to usual care (control) or global intracoronary infusion of CAP-1002 (75 million cells). Read More

Neuroepidemiology 2019 Jan 18;52(3-4):128-135. Epub 2019 Jan 18.

Department of Neurology, Auckland City Hospital, Auckland, New Zealand.

Background: Previous epidemiological studies of genetic muscle disorders have relied on medical records to identify cases and may be at risk of selection biases or have focused on selective population groups.

Objectives: This study aimed to determine age-standardised prevalence of genetic muscle disorders through a nationwide, epidemiological study across the lifespan using the capture-recapture method.

Methods: Adults and children with a confirmed clinical or molecular diagnosis of a genetic muscle disorder, resident in New Zealand on April 1, 2015 were identified using multiple overlapping sources. Read More

Am J Med Genet A 2019 Mar 16;179(3):386-396. Epub 2019 Jan 16.

The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

The ryanodine receptor 1 (RYR1) is a calcium release channel essential for excitation-contraction coupling in the sarcoplasmic reticulum of skeletal muscles. Dominant variants in the RYR1 have been well associated with the known pharmacogenetic ryanodinopathy and malignant hyperthermia. With the era of next-generation gene sequencing and growing number of causative variants, the spectrum of ryanodinopathies has been evolving with dominant and recessive variants presenting with RYR1-related congenital myopathies such as central core disease, minicore myopathy with external ophthalmoplegia, core-rod myopathy, and congenital neuromuscular disease. Read More

F1000Res 2018 11;7. Epub 2018 Dec 11.

Centre for Medical Research, The University of Western Australia, Perth, WA, Australia.

By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Read More

Ann Lab Med 2019 May;39(3):299-310

Department of Rehabilitation Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA).

Methods: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. Read More

Acta Neuropathol Commun 2019 Jan 5;7(1). Epub 2019 Jan 5.

Neuromuscular Morphology Unit, Myology Institute, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.

Several morphological phenotypes have been associated to RYR1-recessive myopathies. We recharacterized the RYR1-recessive morphological spectrum by a large monocentric study performed on 54 muscle biopsies from a large cohort of 48 genetically confirmed patients, using histoenzymology, immunohistochemistry, and ultrastructural studies. We also analysed the level of RyR1 expression in patients' muscle biopsies. Read More

Ethiop J Health Sci 2018 Jul;28(4):513-516

Department of Pediatrics and Child Health, School of Medicine, College of Health Sciences, Addis Ababa University, Ethiopia.

Background: Fibrodysplasia ossificans progressiva (FOP), also known as Myositis ossificans progressiva or Munchmeyer's disease, is an extremely rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO). The disease is characterized by congenital skeletal anomalies and progressive ectopic bone formation in connective tissues such as ligaments, muscles and tendons. The disease has an incidence of about 1 in 2 million population. Read More

J Neuropathol Exp Neurol 2019 Feb;78(2):130-139

Division of Pediatric Pathology, Department of Pathology and Laboratory Medicine.

Mutations in at least 12 genes are responsible for a group of congenital skeletal muscle diseases known as nemaline myopathies (NMs). NMs are associated with a range of clinical symptoms and pathological changes often including the presence of cytoplasmic rod-like structures (nemaline bodies) and myofiber hypotrophy. Our recent work has identified a variable degree of behavioral benefit when treating 2 NM mouse models due to mutations in Acta1 with myostatin inhibition. Read More

Int J Pediatr Otorhinolaryngol 2019 Feb 10;117:26-29. Epub 2018 Nov 10.

Department of Radiology, New York Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, New York, NY, 10065, USA.

A 10-year-old male with history of Beals syndrome presented with hearing loss and was found to have middle and inner ear dysplasia and left temporal encephalocele on imaging. Beals syndrome is a rare autosomal dominant connective tissue disorder caused by a mutation in the fibrillin-2 gene. Skeletal manifestations of Beals have been reported, including anomalies of the long bones, calvarium, and spine. Read More

Eur Respir J 2019 Feb 28;53(2). Epub 2019 Feb 28.

Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, UK.

Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms. Read More

Neuromuscul Disord 2019 Jan 9;29(1):30-38. Epub 2018 Nov 9.

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

Mutations in RYR1 are a common genetic cause of non-dystrophic neuromuscular disorders. To obtain baseline data concerning the prevalence of fatigue, the psychological disease burden and quality of life associated with these common conditions, we performed a questionnaire study. Seventy-two patients were included in this study, 33 with a congenital myopathy and 39 with malignant hyperthermia or exertional rhabdomyolysis. Read More

Neonatal Netw 2018 Jul 1;37(4):212-217. Epub 2018 Jul 1.

Congenital myopathy is an uncommon neonatal disorder that can manifest in the neonatal period with severe features. Presentation with signs of global hypotonia and respiratory insufficiency are among the classic findings. Rapid diagnosis is essential for medical management and family support. Read More

Am J Med Genet A 2019 Feb 18;179(2):317-321. Epub 2018 Dec 18.

Division of Neuromuscular and Neurodegenerative Disorders, IRCCS-Bambino Gesù Children's Hospital, Rome, Italy.

Kyphoscoliotic Ehlers-Danlos syndrome associated with FKBP14 (FKBP14-kEDS) is an ultrarare autosomal recessive disorder reported in less than 30 individuals so far. In its original description, emphasis was put on the mild muscle involvement. Further reports confirm that FKBP14-kEDS is distinguishable from primary muscle disorders by the lack of progressive muscle disease. Read More

BMC Neurol 2018 Dec 15;18(1):207. Epub 2018 Dec 15.

Department of Medical Biology, Hacettepe University Faculty of Medicine, 06100 Sihhiye, Ankara, Turkey.

Background: Alpha-dystroglycan (αDG) is an extracellular peripheral glycoprotein that acts as a receptor for both extracellular matrix proteins containing laminin globular domains and certain arenaviruses. An important enzyme, known as Like-acetylglucosaminyltransferase (LARGE), has been shown to transfer repeating units of -glucuronic acid-β1,3-xylose-α1,3- (matriglycan) to αDG that is required for functional receptor as an extracellular matrix protein scaffold. The reduction in the amount of LARGE-dependent matriglycan result in heterogeneous forms of dystroglycanopathy that is associated with hypoglycosylation of αDG and a consequent lack of ligand-binding activity. Read More

Front Genet 2018 28;9:599. Epub 2018 Nov 28.

Aix-Marseille Univ, INSERM, MMG, U1251, Marseille, France.

Essential muscular organ that provides the whole body with oxygen and nutrients, the heart is the first organ to function during embryonic development. Cardiovascular diseases, including acquired and congenital heart defects, are the leading cause of mortality in industrialized countries. Fibroblast Growth Factors (FGFs) are involved in a variety of cellular responses including proliferation, differentiation, and migration. Read More

Int J Mol Sci 2018 Dec 10;19(12). Epub 2018 Dec 10.

Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.

Point mutations in genes encoding isoforms of skeletal muscle tropomyosin may cause nemaline myopathy, cap myopathy (Cap), congenital fiber-type disproportion (CFTD), and distal arthrogryposis. The molecular mechanisms of muscle dysfunction in these diseases remain unclear. We studied the effect of the E173A, R90P, E150A, and A155T myopathy-causing substitutions in γ-tropomyosin (Tpm3. Read More

PLoS Genet 2018 12 13;14(12):e1007845. Epub 2018 Dec 13.

Institute of Molecular Biology and Medicine, Laboratory Biology of the Cell Nucleus, Université Libre de Bruxelles (ULB), Gosselies, Belgium.

Nucleoporins build the nuclear pore complex (NPC), which, as sole gate for nuclear-cytoplasmic exchange, is of outmost importance for normal cell function. Defects in the process of nucleocytoplasmic transport or in its machinery have been frequently described in human diseases, such as cancer and neurodegenerative disorders, but only in a few cases of developmental disorders. Here we report biallelic mutations in the nucleoporin NUP88 as a novel cause of lethal fetal akinesia deformation sequence (FADS) in two families. Read More

Muscle Nerve 2019 Apr 6;59(4):475-478. Epub 2019 Jan 6.

Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905.

Introduction: Decremental responses in repetitive nerve stimulation have been reported in a few hereditary myopathies. We examined the frequency of decrement in a cohort of myopathy patients.

Methods: We reviewed all patients referred for myopathy who underwent repetitive nerve stimulation between January 2007 and May 2017. Read More

J Forensic Leg Med 2019 Feb 29;61:92-96. Epub 2018 Nov 29.

Department of Legal Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba city, Chiba Prefecture, 260-8670, Japan; Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

A 5-year-old boy with a chromosome-9 abnormality and multiple external and visceral malformations was found in cardiopulmonary arrest during a regular visit to the hospital; he did not respond to cardiopulmonary resuscitation and died. An odontoid process fracture and calcification and fibrosis of the muscles around the superior cervical vertebra were observed during the autopsy. Postmortem computed tomography revealed an anterior dislocation of the atlas; odontoid synchondrosis fracture; and delayed, incomplete bony fusion of the odontoid process relative to his age. Read More

J Dermatol Sci 2018 Dec 20;92(3):245-253. Epub 2018 Nov 20.

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. Electronic address:

Background: ABHD5 mutations cause Chanarin-Dorfman syndrome accompanied by ichthyosis. ω-O-Acylceramide (acylceramide) is essential for skin permeability barrier formation. Acylceramide production is impaired in Abhd5 knockout mice. Read More

Int Heart J 2019 Jan 5;60(1):12-18. Epub 2018 Dec 5.

Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University.

Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Read More

Hum Genet 2019 Jan 27;138(1):105-107. Epub 2018 Nov 27.

Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

ISLR2 (immunoglobulin superfamily containing leucine-rich repeat 2), encodes a protein involved in axon guidance in brain development (hence the other name leucine-rich repeat domain- and immunoglobulin domain-containing axon extension proteins; LINX). A recently described mouse knockout displays hydrocephalus. However, the corresponding phenotype in humans is unknown. Read More

Dermatol Clin 2019 Jan;37(1):95-105

Department of Dermatology, University Hospital "Dr. José E. González", Universidad Autónoma de Nuevo León, Mitras Centro, Avenida Gonzalitos y Madero S/N, Monterrey 64460, Mexico.

Chikungunya and Zika virus infections are emerging diseases in the Americas, and dengue continues to be the most prevalent arthropod-borne virus in the world. These arbovirus diseases may spread by endemic transmission or as travel-related infections and have rapidly expanded their geographic distribution secondary to vector spread. All 3 share a similar clinical picture that includes a maculopapular rash. Read More

Mutat Res 2018 Oct - Dec;778:45-50. Epub 2018 Sep 12.

Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha, PR China. Electronic address:

Protein O-mannosyltransferase 1 (POMT1) is a critical enzyme participating in the first step of protein O-mannosylation. Mutations in the coding gene, POMT1, have been described to be related to a series of autosomal recessive disorders associated with defective alpha-dystroglycan glycosylation, later termed muscular dystrophy-dystroglycanopathies (MDDGs). MDDGs are characterized by a broad phenotypic spectrum of congenital muscular dystrophy or later-onset limb-girdle muscular dystrophy, accompanied by variable degrees of intellectual disability, brain defects, and ocular abnormalities. Read More