25 results match your criteria: "Finland (B.U.); Hospital Universitario HM Puerta del Sur[Affiliation]"
-Related Muscular Dystrophies, LGMD, and TMD, in an Estonian Family Caused by the Finnish Founder Variant.
Neurol Genet
December 2024
From the The Institute of Clinical Medicine (K.Õ., T.R., E.Õ.-S., L.M., S. Pajusalu), Faculty of Medicine, University of Tartu; Genetics and Personalized Medicine Clinic (K.Õ., T.R., L.M., Sander Pajusalu); Children's Clinic (E.O.-S.); Pathology Department (S. Puusepp), Tartu University Hospital, Estonia; Folkhalsan Research Center (M.S., B.U.), Helsinki; and Tampere Neuromuscular Center (B.U.), Tampere, Finland.
Background And Objectives: Tibial muscular dystrophy (TMD) is an autosomal dominant, slowly progressive late-onset distal myopathy. TMD was first described in 1991 by Udd et al. in Finnish patients, who were later found to harbor a heterozygous unique 11-bp insertion/deletion in the last exon of the gene-the Finnish founder variant (FINmaj).
View Article and Find Full Text PDFA Titin Truncating Variant Causing a Dominant Myopathy With Cardiac Involvement in a Large Family: The Exception That Proves the Rule.
Neurol Genet
October 2024
From the Department of Neurology (K.G.C.), University Hospitals Leuven; Department of Neurosciences (K.G.C.), Laboratory for Muscle Diseases and Neuropathies, KU Leuven, and Leuven Brain Institute (LBI), Belgium; Folkhälsan Research Center and Medicum (M.S., P.H.J., A.V., B.U.), University of Helsinki, Finland; Department of Radiology (V.G.), University Hospitals Leuven, Belgium; John Walton Muscular Dystrophy Research Centre (A.T., V.S.), Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Neuromuscular Research Center (B.U.), Department of Neurology, Tampere University and University Hospital; and Department of Neurology (B.U.), Vaasa Central Hospital, Finland.
Background: Titin truncating variants (TTNtvs) have been repeatedly reported as causative of recessive but not dominant skeletal muscle disorders.
Objective: To determine whether a single heterozygous nonsense variant in can be responsible for the observed dominant myopathy in a large family.
Methods: In this case series, all available family members (8 affected and 6 healthy) belonging to a single family showing autosomal dominant inheritance were thoroughly examined clinically and genetically.
Homozygosity of a Founder Variant c.1508dupC in Causes Congenital Myasthenia With Variable Severity.
Neurol Genet
June 2024
From the Neuromuscular Research Center (J.P., S.P., B.U.), Tampere University and University Hospital, Neurology; The Finnish Medical Society Duodecim (P.K.), Helsinki; Department of Pediatrics (P.K.), Kuopio University Hospital, and University of Eastern Finland Kuopio; Neurocenter (P.H.H.), Neurology, Kuopio University Hospital; Department of Child Neurology (P.I.), Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital; Research Programs Unit (P.I.), Stem Cells and Metabolism, University of Helsinki; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital; Department of Pediatric Neurology (K.V.); Department of Genetics (S.L.), Fimlab Laboratories, Tampere University Hospital; Department of Pediatric Neurology (J.K.), Kuopio University Hospital; Department of Neurology (S.H., K.P.), Central Finland Central Hospital, Jyväskylä; Institute for Molecular Medicine Finland FIMM (J.S.), University Helsinki, Finland; Centre for Molecular Medicine Norway (J.S.), University of Oslo, Norway; Folkhälsan Institute of Genetics and the Department of Medical Genetics (B.U.), Haartman Institute, University of Helsinki; and Department of Neurology (B.U.), Vaasa Central Hospital, Finland.
Background And Objectives: Description of 15 patients with the same variant in causing congenital myasthenic syndrome (CMS).
Methods: Nine adult and 6 pediatric patients were studied with molecular genetic and clinical investigations.
Results: All patients were identified with the c.
Variant Associated With a Myalgic Myopathy Phenotype.
Neurology
October 2023
From the Department of Neurology (V.P., P.H.), Kuopio University Hospital; Tampere Neuromuscular Center (J.P., M.J., A.V., B.U.); Tampere University Hospital (J.P.); Tampere University (J.P.); Neurology (M.J.), Clinical Medicine, University of Turku; Neurocenter (M.J.), Turku University Hospital; Folkhälsan Research Center (A.V., B.U.), Helsinki; Medicum (A.V., B.U.), University of Helsinki; Fimlab Laboratories (A.V.), Tampere; Department of Pathology (T.R.), Kuopio University Hospital; and Unit of Pathology (T.R.), Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
Background And Objectives: This study aimed to characterize the phenotype of a novel myalgic myopathy encountered in a Finnish family.
Methods: Four symptomatic and 3 asymptomatic individuals from 2 generations underwent clinical, neurophysiologic, imaging, and muscle biopsy examinations. Targeted sequencing of all known myopathy genes was performed.
Author Correction: A consensus protocol for functional connectivity analysis in the rat brain.
Nat Neurosci
June 2023
Institute of Experimental and Clinical Pharmacology and Toxicology, FAU Erlangen-Nürnberg, Erlangen, Germany.
A consensus protocol for functional connectivity analysis in the rat brain.
Nat Neurosci
April 2023
Institute of Experimental and Clinical Pharmacology and Toxicology, FAU Erlangen-Nürnberg, Erlangen, Germany.
Article Synopsis
- * It introduces StandardRat, a standardized fMRI acquisition protocol for rats that has been tested across 20 research centers to enhance data integration.
- * The standardized protocol and processing pipeline improve the reliability of detecting functional connectivity patterns and are made publicly available to foster collaboration in the neuroimaging field.
Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age.
N Engl J Med
February 2023
From Texas Children's Hospital, Baylor College of Medicine, Houston (F.M.M.), and the University of Texas Medical Branch, Galveston (J.Z., X. Xie, P.-Y.S.); Peninsula Research Associates, Rolling Hills Estates (L.D.S.), and Stanford University School of Medicine, Palo Alto (Y.M.) - both in California; Vaccine Research and Development, Pfizer, Pearl River (C.S., A.G., U.N.S., C.H., M.I., B.A.P., I.M., K.A.S., K.K., C.L., D.C., K.U.J., W.C.G.), and SUNY Upstate Medical University, Syracuse (J.B.D.) - both in New York; Vaccine Research and Development (X. Xu, H.M.), and Worldwide Safety, Safety Surveillance and Risk Management (S.M.), Pfizer, Collegeville, PA; Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., C.W., L.C.); Atlanta Center for Medical Research, Atlanta (R.R.); Spring Valley Pediatrics, Washington, DC (J.M.S.); Katedra Pediatrii, Instytut Nauk Medycznych, Kolegium Nauk Medycznych, Uniwersytet Rzeszowski, Rzeszow, Poland (H.C.); the Department of Pediatrics, University of Cincinnati College of Medicine, and the Division of Pediatric Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati (G.C.P.); Duke Human Vaccine Institute, Durham, NC (E.B.W.); Johns Hopkins University, Baltimore (K.R.T.); Seattle Children's Hospital, Seattle (J.A.E.); Tampere University, Espoo Vaccine Research Clinic, Espoo, Finland (B.U.); Hospital Universitario HM Puerta del Sur, Madrid (S.N.M.); and BioNTech, Mainz, Germany (Ö.T., U.Ş.).
Background: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children.
Methods: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy).
Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the Gene.
Neurol Genet
December 2021
Folkhälsan Research Center (P.H., S.M.R., M.J., A.V., P.H.J., J.S., S.K., H.L., M.S., M.A., M.S., B.U.); University of Helsinki (S.M.R., M.J., A.V., P.H.J., J.S., S.K., H.L., M.S., M.A., M.S.), Helsinki; Finnish Neuromuscular Center, Fimlab Laboratories and Tampere University (A.V.); Institute for Molecular Medicine Finland (FIMM), University of Helsinki (K.D., P.L.); MRC, University of Oulu, Oulu (I.M.); Pietarsaari Hospital, Pietarsaari, Finland (I.M.); Clinical Neurosciences, Neurology, Helsinki University Hospital (M.A.); Vaasa Central Hospital (B.U.), Vaasa, Finland.
Background And Objectives: To determine the genetic cause of the disease in the previously reported family with adult-onset autosomal dominant distal myopathy (myopathy, distal, 3; MPD3).
Methods: Continued clinical evaluation including muscle MRI and muscle pathology. A linkage analysis with single nucleotide polymorphism arrays and genome sequencing were used to identify the genetic defect, which was verified by Sanger sequencing.
Out-of-Frame Mutations in Last Exon Cause a Dominant Distal Myopathy With Facial Weakness.
Neurol Genet
October 2021
Folkhälsan Research Center (M. Savarese, A.V., M.J., P.H.J., P.H., B.U.), Helsinki; Department of Medical Genetics (M. Savarese, A.V., M.J., P.H.J., P.H., B.U.), Medicum, University of Helsinki; Neuromuscular Research Center (A.V.), Department of Genetics, Fimlab Laboratories, Tampere; Division of Clinical Neurosciences (M.E.J.), Department of Neurology, Turku University and University Hospital; Neuromuscular Research Center (S.P.H.), Department of Pathology, Fimlab Laboratories, Tampere, Finland; Neuroradiology Unit (S.G.), ASST Papa Giovanni XXIII, Bergamo; Dipartimento di Medicina di Precisione (A.T., M.E.O., V.N.), Università degli Studi della Campania "Luigi Vanvitelli," Napoli; Telethon Institute of Genetics and Medicine (A.T., V.N.), Pozzuoli; Division of Neuroscience and U.O. Neurologia (M. Scarlato, S.C.P.), IRCCS Ospedale San Raffaele, Milano, Italy; Randall Centre for Cell and Molecular Biophysics (M.G.), King's College London BHF Centre of Research Excellence, United Kingdom; Department of Neurology (B.U.), Vaasa Central Hospital; and Neuromuscular Research Center (M.E.J., B.U.), Department of Neurology, Tampere University and University Hospital, Finland.
Background And Objectives: To clinically, genetically, and histopathologically characterize patients presenting with an unusual combination of distal myopathy and facial weakness, without involvement of upper limb or shoulder girdle muscles.
Methods: Two families with a novel form of actininopathy were identified. Patients had been followed up over 10 years.
Metabolic Traits and Stroke Risk in Individuals of African Ancestry: Mendelian Randomization Analysis.
Stroke
August 2021
Department of Epidemiology and Biostatistics, Medical School Building, St Mary's Hospital, Imperial College London, United Kingdom (V.K., M.-R.J., D.G.).
Background And Purpose: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals.
Methods: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061).
New family with 8-associated autosomal dominant rimmed vacuolar myopathy.
Neurol Genet
August 2019
Division of Genetics and Genomic Medicine (S.A.-T., L.W., H.Y.), Department of Pediatrics, University of California, Irvine; Opti West (S.A.-T.), West Anaheim Medical Center, Anaheim; Ambry Genetics (S.T.), Mission Viejo, CA; Miller School of Medicine (M.S.), University of Miami, FL; Folkhälsan Institute of Genetics and the Department of Medical Genetics (A.V., B.U.), Medicum, University of Helsinki; Neuromuscular Research Center (A.V., B.U.), Tampere University and University Hospital, Neurology, Finland; Neuromuscular Program (T.M.), Department of Neurology, University of California-Irvine, Orange; and Neurology Department (B.U.), Vasa Central Hospital, Finland.
Article Synopsis
- A new family with autosomal dominant rimmed vacuolar myopathy (RVM) was studied, revealing that the disorder is linked to a specific mutation in the gene.
- Whole-exome and whole-genome sequencing were utilized alongside muscle biopsies and imaging techniques, showing typical symptoms like muscle atrophy and fatty changes in the muscles.
- The identified mutation (c.515dupC) caused a frameshift that results in a longer protein, affecting the expression of heat shock protein beta 8 and disrupting autophagy, which could lead to future targeted treatment strategies for RVM.*
Novel mutation in causes congenital limb-girdle myopathy with slow progression.
Neurol Genet
June 2019
Folkhälsan Institute of Genetics and Department of Medical Genetics (A.V.), Medicum, University of Helsinki; Neuromuscular Research Center (J.P.), Tampere University and University Hospital of Tampere, Finland; Neuromuscular Unit (O.D.), Division of Neurology, Department of Clinical and Experimental Medicine, Linköping University, Sweden; Neuromuscular Research Center (S. Penttilä), Tampere University and University Hospital of Tampere, Finland; Department of Neurology (D.L.), Department of Neurology (S. Pittman), Department of Neurology (C.W.), Washington University School of Medicine, Saint Louis, MO; Folkhälsan Institute of Genetics and Department of Medical Genetics (B.U.), Medicum, University of Helsinki; Neuromuscular Research Center (B.U.), Tampere University and University Hospital of Tampere; and Department of Neurology (B.U.), Vaasa Central Hospital, Vaasa, Finland.
Objective: We report a second family with autosomal dominant transportinopathy presenting with congenital or early-onset myopathy and slow progression, causing proximal and less pronounced distal muscle weakness.
Methods: Patients had clinical examinations, muscle MRI, EMG, and muscle biopsy studies. The MYOcap gene panel was used to identify the gene defect in the family.
Oligogenic basis of sporadic ALS: The example of p.Ala90Val mutation.
Neurol Genet
June 2019
Department of Clinical Genetics (L.K.), Helsinki University Hospital; Department of Medical Genetics (L.K.), University of Helsinki, Helsinki, Finland; Molecular Neurology (K.K., M.V., P.J.T.), Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland; Department of Medical Genetics (S.M.), University of Helsinki, Helsinki, Finland and Turku; University Hospital (S.M.), Laboratory Division, Genetics and Saske, Department of Medical Genetics, Turku, Finland; Department of Neurology (H.L.), Helsinki University Hospital, and Molecular Neurology, Research Programs Unit, Biomedicum, University of Helsinki, Helsinki, Finland; Neuromuscular Research Center (M.J., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Division of Clinical Neurosciences (M.J.), Turku University Hospital and University of Turku, Turku, Finland; Folkhälsan Research Center (B.U.), Biomedicum, University of Helsinki, Helsinki, Finland; Institute of Biomedicine (P.P., J.S.), University of Turku; Turku University Hospital (P.P., J.S.), Laboratory Division, Genetics and Saske, Department of Medical Genetics, Turku, Finland; Department of Pathology (A.P.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Laboratory of Neurogenetics (B.J.T.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Merck & Co. (D.J.S.), Inc., West Point, PA; Department of Clinical Genetics (M.P.), Helsinki University Hospital; Department of Medical Genetics (M.P.), University of Helsinki, Helsinki, Finland; Department of Neurology (P.J.T.), Helsinki University Hospital; and Department of Pathology (L.M.), University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Objective: To characterize the clinical and neuropathologic features of patients with amyotrophic lateral sclerosis (ALS) with the superoxide dismutase 1 () p.Ala90Val mutation, as well as the mutation frequency and the role of oligogenic mechanisms in disease penetrance.
Methods: An index patient with autopsy-proven ALS was discovered to have the p.
An unusual ryanodine receptor 1 (RYR1) phenotype: Mild calf-predominant myopathy.
Neurology
April 2019
From the Neuromuscular Research Center (M. Jokela, S.L., J.P., B.U.), Department of Neurology, University Hospital and University of Tampere; Division of Clinical Neurosciences (M. Jokela), Department of Neurology, Turku University Hospital and University of Turku; Kiinamyllynkatu 4-8 (M. Jokela), Turku, Finland; Unità Operativa Complessa di Neurologia (G.T.), Dipartimento di Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Folkhälsan Institute of Genetics and Department of Medical Genetics (A.V., P.-H.J., S.V., M. Johari, M.S.), Haartman Institute, University of Helsinki, Finland; Institute of Pediatric Neurology (E.M., M.P.), Catholic University School of Medicine, Rome, Italy; Department of Pathology (S.H.), Fimlab Laboratories, Tampere University Hospital, Finland; Metabolic and Neuromuscular Unit (M.D.), Meyer Hospital, Florence, Italy; Department of Pediatric Neurology (P.I.), Children's Hospital, University of Helsinki and Helsinki University Hospital; Department of Neurology (P.H.), Kuopio University Hospital and University of Eastern Finland; and Department of Neurology (B.U.), Vasa Central Hospital, Finland.
Objective: To identify the genetic defect causing a distal calf myopathy with cores.
Methods: Families with a genetically undetermined calf-predominant myopathy underwent detailed clinical evaluation, including EMG/nerve conduction studies, muscle biopsy, laboratory investigations, and muscle MRI. Next-generation sequencing and targeted Sanger sequencing were used to identify the causative genetic defect in each family.
Clinical Reasoning: A 54-year-old man with dyspnea and muscle weakness.
Neurology
March 2019
From the Departments of Neurology (A.C., M.S., L.B., F.P., L.L.C., R.R.) and Respiratory Medicine (E.B.), Hospital Británico de Buenos Aires, Argentina; Folkhälsan Institute of Genetics (B.U.), Helsinki University; Tampere Neuromuscular Center (B.U.), Tampere University and University Hospital; and Neurology Department (B.U.), Vaasa Central Hospital, Vaasa, Finland.
Myasthenic congenital myopathy from recessive mutations at a single residue in Na1.4.
Neurology
March 2019
From the Departments of Physiology (N.E., M.Q., S.C.C.) and Neurology (P.B.S.), David Geffen School of Medicine at UCLA; Molecular and Cellular Integrative Physiology Program at UCLA (N.E., S.C.C.), Los Angeles, CA; Tampere Neuromuscular Center (J.P., T.S., B.U.), Tampere University and University Hospital, Finland; MRC Centre for Neuromuscular Diseases (M.S.C., M.G.H., R.M.), Department of Neuromuscular Disease, UCL Institute of Neurology, London, UK; Folkhälsan Genetic Institute (B.U.), Helsinki; and Neurology Department (B.U.), Vasa Central Hospital, Finland.
Objective: To identify the genetic and physiologic basis for recessive myasthenic congenital myopathy in 2 families, suggestive of a channelopathy involving the sodium channel gene, .
Methods: A combination of whole exome sequencing and targeted mutation analysis, followed by voltage-clamp studies of mutant sodium channels expressed in fibroblasts (HEK cells) and oocytes.
Results: Missense mutations of the same residue in the skeletal muscle sodium channel, R1460 of Na1.
Copy number variation analysis increases the diagnostic yield in muscle diseases.
Neurol Genet
December 2017
Folkhälsan Institute of Genetics (S.V., M.S., M.J., L.S., M.A., K.K., K.P., B.U., P.H.), Medicum, Faculty of Biological and Environmental Sciences (K.P.), University of Helsinki, Finland; Neuromuscular Research Center (B.U.), Tampere University and University Hospital, Finland; Department of Neurology (B.U.), Vaasa Central Hospital, Finland; Biodonostia Health Research Institute (A.S., A.L.D.M), Neurosciences Area, CIBERNED, University of the Basque Country, San Sebastián, Spain; and Centre de Référence Maladies Neuromusculaires (GNMH) (A.-M.C.), Hôpital Marin APHP, Hendaye, France.
Objective: Copy number variants (CNVs) were analyzed from next-generation sequencing data, with the aim of improving diagnostic yield in skeletal muscle disorder cases.
Methods: Four publicly available bioinformatic analytic tools were used to analyze CNVs from sequencing data from patients with muscle diseases. The patients were previously analyzed with a targeted gene panel for single nucleotide variants and small insertions and deletions, without achieving final diagnosis.
Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in gene.
Neurology
April 2017
From the Neuromuscular Research Center (J.P., S.P., B.U.), Department of Neurology, Tampere University and University Hospital, Neurology; Seinäjoki Central Hospital (S.S.), Department of Neurology, Finland; MRC Centre for Neuromuscular Disease (M.G.H., R.M.), UCL Institute of Neurology, Queen Square, London, UK; Folkhälsan Institute of Genetics and the Department of Medical Genetics (B.U.), Haartman Institute, University of Helsinki; and Vaasa Central Hospital (B.U.), Department of Neurology, Finland.
Objective: To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation.
Methods: Twenty-nine Finnish patients identified with the c.
Epidermolysis bullosa simplex with muscular dystrophy associated with deletion mutation.
Neurol Genet
December 2016
Instituto de Investigaciones Médicas Dr. A. Lanari (V.C.A., V.L.S., C.G.M.), Buenos Aires, Argentina; Neuromuscular Research Center (S.T.P., B.U.), Tampere University and University Hospital, Folkhälsan Genetic Institute (B.U.), and Vasa Central Hospital (B.U.), Finland.
Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disorder characterized by neonatal blistering and later-onset muscle weakness.
View Article and Find Full Text PDFThe genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients.
Neurology
July 2016
From the Dipartimento di Biochimica Biofisica e Patologia Generale (M.S., G.D.F., A. Torella, A.G., T.G., F.D.V.B., G.E., G.P., V.N.), Seconda Università di Napoli; Telethon Institute of Genetics and Medicine (M.S., G.D.F., A. Torella, M. Mutarelli, V.S.M., A.G., T.G., G.E., V.N.), Pozzuoli; U.O.C. Neurologia Pediatrica e Malattie Muscolari (C.F., C.M., C.B.), IRCCS Istituto Giannina Gaslini, Genova; Centro Dino Ferrari, Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti (F.M., D.R., G.P.C.), and Neuromuscular and Rare Disease Unit, Dipartimento di Neuroscienze (M. Moggio), Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan; Dipartimento di Neuroscienze (M. Fanin, E.P.), Università di Padova; Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche (L.R., L.S.), Università degli Studi di Napoli "Federico II," Napoli; Dipartimento di Medicina Clinica e Sperimentale (G.R., G.S.), Università degli Studi di Pisa; Medicina Molecolare (G.A., F.M.S.), IRCCS Fondazione Stella Maris, Pisa; Dipartimento di Medicina Sperimentale (L. Passamano, P.D., R.P., L. Politano) and Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche, e dell'Invecchiamento (O.F., S.S., G.D.I.), Seconda Università di Napoli; Dipartimento di Neuroscienze (A.R., M. Mora, L.M.), Istituto Besta, Milano; Don Carlo Gnocchi ONLUS Foundation (G.T.), Milano; Dipartimento di Neuroscienze (A.D., E.B.), IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy; Center for Medical Genetics (S.J., K.C.) and Department of Neurology (J.D.B.), Ghent University Hospital, Belgium; Dipartimento di Neuroscienze (O.M., C.R., S.M., A. Toscano), Università degli Studi di Messina, Italy; Folkhälsan Institute of Genetics (A.E., P.H., B.U.), University of Helsinki, Finland; Section for Neuromuscular Diseases and Neuropathies (M. Filosto), Unit of Clinical Neurology, University Hospital 'Spedali Civili,' Brescia, Italy; Neuromusc
Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients.
Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy.
PFKM gene defect and glycogen storage disease GSDVII with misleading enzyme histochemistry.
Neurol Genet
June 2015
Research Programs Unit (M.A., E.Y., H.T.), Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland; Clinical Neurosciences (M.A.), Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Neuromuscular Research Center (J.P., S.S., K.V., B.U.), Tampere University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (S.H., H.H.), Fimlab Laboratories, University Hospital and University of Tampere, Tampere, Finland; Department of Pathology (A.P.), HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neurology (S.S.), Seinäjoki Central Hospital, Seinäjoki, Finland; and Unit of Clinical Physiology (P.P.), HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland.
Objective: To elaborate the diagnostic methods used as "gold standard" in one of the most common glycogen storage diseases (GSDs), Tarui disease (GSDVII).
Methods: Two siblings with disease suggestive of GSD underwent thorough clinical analysis, including muscle biopsy, muscle MRI, exercise tests, laboratory examinations, and whole-exome sequencing (WES).
Results: Both siblings had juvenile-onset exercise intolerance with cramping and infrequent myoglobinuria.
Mutations in HSPB8 causing a new phenotype of distal myopathy and motor neuropathy.
Neurology
January 2016
From the Institute for Neuroscience and Muscle Research (R.G., L.W., S.K., N.C.), Kids Research Institute, Children's Hospital at Westmead & University of Sydney, Australia; Neuromuscular Research Center, Department of Neurology (J.P., S.P., M.L., B.U.), and Department of Pathology, Fimlab Laboratories (S.H.), Tampere University Hospital and University of Tampere, Finland; Department of Pathology (J.B.), Royal North Shore Hospital, Sydney, Australia; Broad Institute of Harvard and MIT (M.L., D.G.M.), Cambridge, MA; Western Australian Neurosciences Research Institute (M.N.), University of Western Australia, Perth; Folkhälsan Institute of Genetics and Department of Medical Genetics (A.E., P.H., P.H.-J., A.V., B.U.), University of Helsinki, Finland; Department of Neurogenetics (R.L.D., C.Y., C.M.S.), Kolling Institute, Royal North Shore Hospital and University of Sydney; Murdoch Children's Research Institute (K.N.), The Royal Children's Hospital, Melbourne, Australia; Analytic and Translational Genetics Unit (M.L., D.G.M.), Massachusetts General Hospital, Boston; and Department of Neurology (B.U.), Vaasa Central Hospital, Finland.
Objective: To report novel disease and pathology due to HSPB8 mutations in 2 families with autosomal dominant distal neuromuscular disease showing both myofibrillar and rimmed vacuolar myopathy together with neurogenic changes.
Methods: We performed whole-exome sequencing (WES) in tandem with linkage analysis and candidate gene approach as well as targeted next-generation sequencing (tNGS) to identify causative mutations in 2 families with dominant rimmed vacuolar myopathy and a motor neuropathy. Pathogenic variants and familial segregation were confirmed using Sanger sequencing.
A new titinopathy: Childhood-juvenile onset Emery-Dreifuss-like phenotype without cardiomyopathy.
Neurology
December 2015
From INSERM (R.D.C., C.R., K.C., I.R.), U951; Généthon (R.D.C., C.R., K.C., I.R.), R&D Department, INTEGRARE Research Unit, Evry; Neuromuscular Morphology Unit, Myology Institute (N.B.R., M.B.), and INSERM UMRS_974, CNRS FRE 3617, Center of Research in Myology (R.B.Y., F.L., N.B.R., E.M., M.B., I.N., G.B.), Sorbonne Universités, UPMC Univ Paris 06, and AP-HP, University Hospital, Reference Center for Neuromuscular Diseases, Myology Institute (R.B.Y., N.B.R., E.M., B.E.), Groupe Hospitalier La Pitié-Salpêtrière, Paris; Génopole Campus 2 (S.B., A.C.), PartnerChip, Evry; the Department of Medical Genetics (F.L., A.V., B.U.), Folkhälsan Institute of Genetics, University of Helsinki, Finland; AP-HP (J.N.), Groupe Hospitalier Cochin-Broca-Hôtel Dieu, Laboratoire de Biochimie et Génétique Moléculaire, Paris; CEA-IG-Centre National de Genotypage (L.B.A., C.C., R.O.), Evry; Neuromuscular Research Center (B.U.), Tampere University Hospital and University of Tampere, Finland; and the Department of Neurology (B.U.), Vaasa Central Hospital, Finland. R.D.C. is currently affiliated with Disease Genomics Group, Institut de Medicina Predictiva i Personalitzada del Càncer, Campus de Can Ruti, Camí de les Escoles, Badalona (Barcelona), Spain.
Objective: To identify the genetic defects present in 3 families with muscular dystrophy, contractures, and calpain 3 deficiency.
Methods: We performed targeted exome sequencing on one patient presenting a deficiency in calpain 3 on Western blot but for which mutations in the gene had been excluded. The identification of a homozygous truncating mutation in the M-line part of titin prompted us to sequence this region in 2 additional patients presenting similar clinical and biochemical characteristics.
SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles.
Neurology
August 2015
From the Department of Neurology (R.C.B., K.A., A.P., S.K.P., M.B.H., C.C.W.), Washington University School of Medicine, Saint Louis, MO; Dent Neurologic Institute (L.R.), Amherst, NY; Department of Neurogenetics (C.M.S.), Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St Leonard's, New South Wales, Australia; Folkhalsan Institute of Genetics and Department of Medical Genetics (A.E., P.H., B.U.), Haartman Institute, University of Helsinki, Finland; Neuromuscular Research Center (B.U.), Tampere University Hospital and University of Tampere, Finland; and Department of Neurology (B.U.), Vaasa Central Hospital, Vaasa, Finland.
Objective: To identify the genetic etiology and characterize the clinicopathologic features of a novel distal myopathy.
Methods: We performed whole-exome sequencing on a family with an autosomal dominant distal myopathy and targeted exome sequencing in 1 patient with sporadic distal myopathy, both with rimmed vacuolar pathology. We also evaluated the pathogenicity of identified mutations using immunohistochemistry, Western blot analysis, and expression studies.
Long-term exposure to enhanced ultraviolet-B radiation in the sub-arctic does not cause oxidative stress in Vaccinium myrtillus.
New Phytol
December 1998
Department of Plant Physiology, University of Lund, P.O. Box 117, S-22100, Lund, Sweden.
The aim of this work was to assess whether or not oxidative stress had developed in a dwarf shrub bilberry (Vaccinium myrtillus L.) under long-term exposure to enhanced levels of ultraviolet-B (u.v.
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