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Digenic inheritance involving a muscle-specific protein kinase and the giant titin protein causes a skeletal muscle myopathy.
Töpf, Ana; Cox, Dan; Zaharieva, Irina T; Di Leo, Valeria; Sarparanta, Jaakko; Jonson, Per Harald; Sealy, Ian M; Smolnikov, Andrei; White, Richard J; Vihola, Anna; Savarese, Marco; Merteroglu, Munise; Wali, Neha; Laricchia, Kristen M; Venturini, Cristina; Vroling, Bas; Stenton, Sarah L; Cummings, Beryl B; Harris, Elizabeth; Marini-Bettolo, Chiara; Diaz-Manera, Jordi; Henderson, Matt; Barresi, Rita; Duff, Jennifer; England, Eleina M; Patrick, Jane; Al-Husayni, Sundos; Biancalana, Valerie; Beggs, Alan H; Bodi, Istvan; Bommireddipalli, Shobhana; Bönnemann, Carsten G; Cairns, Anita; Chiew, Mei-Ting; Claeys, Kristl G; Cooper, Sandra T; Davis, Mark R; Donkervoort, Sandra; Erasmus, Corrie E; Fassad, Mahmoud R; Genetti, Casie A; Grosmann, Carla; Jungbluth, Heinz; Kamsteeg, Erik-Jan; Lornage, Xavière; Löscher, Wolfgang N; Malfatti, Edoardo; Manzur, Adnan; Martí, Pilar; Mongini, Tiziana E.
Afiliación
  • Töpf A; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK. ana.topf@ncl.ac.uk.
  • Cox D; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Zaharieva IT; Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & Great Ormond Street Hospital, London, UK.
  • Di Leo V; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Sarparanta J; Department of Life Sciences, University of Trieste, Trieste, Italy.
  • Jonson PH; Folkhälsan Research Center, Helsinki, Finland.
  • Sealy IM; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
  • Smolnikov A; Folkhälsan Research Center, Helsinki, Finland.
  • White RJ; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
  • Vihola A; School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
  • Savarese M; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
  • Merteroglu M; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
  • Wali N; School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
  • Laricchia KM; Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.
  • Venturini C; Folkhälsan Research Center, Helsinki, Finland.
  • Vroling B; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
  • Stenton SL; Neuromuscular Research Centre, Tampere University and University Hospital, Tampere, Finland.
  • Cummings BB; Folkhälsan Research Center, Helsinki, Finland.
  • Harris E; Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
  • Marini-Bettolo C; School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK.
  • Diaz-Manera J; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padua, Padua, Italy.
  • Henderson M; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Barresi R; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Duff J; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • England EM; Division of Infection and Immunity, University College London, London, UK.
  • Patrick J; Bio-Prodict, Nijmegen, The Netherlands.
  • Al-Husayni S; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Biancalana V; Division of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, Boston, MA, USA.
  • Beggs AH; Laboratory of Angiogenesis and Cancer Metabolism, Department of Biology, University of Padua, Padua, Italy.
  • Bodi I; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Bommireddipalli S; Northern Genetics Service, Institute of Genetics Medicine, Newcastle upon Tyne, UK.
  • Bönnemann CG; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Cairns A; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Chiew MT; Muscle Immunoanalysis Unit, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Claeys KG; IRCCS San Camillo Hospital, Venice, Italy.
  • Cooper ST; John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
  • Davis MR; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Donkervoort S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
  • Erasmus CE; The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Fassad MR; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U1258, Cnrs UMR7104, Université de Strasbourg, Illkirch, France.
  • Genetti CA; The Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Grosmann C; Department of Clinical Neuropathology, King's College Hospital NHS Foundation Trust, London, UK.
  • Jungbluth H; Kids Neuroscience Centre, the Children's Hospital at Westmead, the University of Sydney and the Children's Medical Research Institute, Westmead, New South Wales, Australia.
  • Kamsteeg EJ; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
  • Lornage X; Neurosciences Department, Queensland Children's Hospital, Brisbane, Queensland, Australia.
  • Löscher WN; Department of Diagnostic Genomics, PathWest Laboratory Medicine, Perth, Western Australia, Australia.
  • Malfatti E; Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
  • Manzur A; Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium.
  • Martí P; Kids Neuroscience Centre, the Children's Hospital at Westmead, the University of Sydney and the Children's Medical Research Institute, Westmead, New South Wales, Australia.
  • Mongini TE; Department of Diagnostic Genomics, PathWest Laboratory Medicine, Perth, Western Australia, Australia.
Nat Genet ; 56(3): 395-407, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38429495
ABSTRACT
In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Enfermedades Musculares Límite: Animals / Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Enfermedades Musculares Límite: Animals / Humans / Male Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido