Browsing by Subject "ALPHA-DYSTROGLYCAN"

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  • Johnson, Katherine; Bertoli, Marta; Phillips, Lauren; Topf, Ana; Van den Bergh, Peter; Vissing, John; Witting, Nanna; Nafissi, Shahriar; Jamal-Omidi, Shirin; Lusakowska, Anna; Kostera-Pruszczyk, Anna; Potulska-Chromik, Anna; Deconinck, Nicolas; Wallgren-Pettersson, Carina; Strang-Karlsson, Sonja; Colomer, Jaume; Claeys, Kristl G.; De Ridder, Willem; Baets, Jonathan; von der Hagen, Maja; Fernandez-Torron, Roberto; Zulaica Ijurco, Miren; Espinal Valencia, Juan Bautista; Hahn, Andreas; Durmus, Hacer; Willis, Tracey; Xu, Liwen; Valkanas, Elise; Mullen, Thomas E.; Lek, Monkol; MacArthur, Daniel G.; Straub, Volker (2018)
    Background: Dystroglycanopathies are a clinically and genetically heterogeneous group of disorders that are typically characterised by limb-girdle muscle weakness. Mutations in 18 different genes have been associated with dystroglycanopathies, the encoded proteins of which typically modulate the binding of alpha-dystroglycan to extracellular matrix ligands by altering its glycosylation. This results in a disruption of the structural integrity of the myocyte, ultimately leading to muscle degeneration. Methods: Deep phenotypic information was gathered using the PhenoTips online software for 1001 patients with unexplained limb-girdle muscle weakness from 43 different centres across 21 European and Middle Eastern countries. Whole-exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. Genes known to be associated with dystroglycanopathies were analysed for disease-causing variants. Results: Suspected pathogenic variants were detected in DPM3, ISPD, POMT1 and FKTN in one patient each, in POMK in two patients, in GMPPB in three patients, in FKRP in eight patients and in POMT2 in ten patients. This indicated a frequency of 2.7% for the disease group within the cohort of 1001 patients with unexplained limb-girdle muscle weakness. The phenotypes of the 27 patients were highly variable, yet with a fundamental presentation of proximal muscle weakness and elevated serum creatine kinase. Conclusions: Overall, we have identified 27 patients with suspected pathogenic variants in dystroglycanopathy-associated genes. We present evidence for the genetic and phenotypic diversity of the dystroglycanopathies as a disease group, while also highlighting the advantage of incorporating next-generation sequencing into the diagnostic pathway of rare diseases.
  • Korzyukov, Yegor; Iheozor-Ejiofor, Rommel; Levanov, Lev; Smura, Teemu; Hetzel, Udo; Szirovicza, Leonora; de la Torre, Juan Carlos; Martinez-Sobrido, Luis; Kipar, Anja; Vapalahti, Olli; Hepojoki, Jussi (2020)
    Reptarenaviruses cause Boid Inclusion Body Disease (BIBD), and co-infections by several reptarenaviruses are common in affected snakes. Reptarenaviruses have only been found in captive snakes, and their reservoir hosts remain unknown. In affected animals, reptarenaviruses appear to replicate in most cell types, but their complete host range, as well as tissue and cell tropism are unknown. As with other enveloped viruses, the glycoproteins (GPs) present on the virion's surface mediate reptarenavirus cell entry, and therefore, the GPs play a critical role in the virus cell and tissue tropism. Herein, we employed single cycle replication, GP deficient, recombinant vesicular stomatitis virus (VSV) expressing the enhanced green fluorescent protein (scrVSV Delta G-eGFP) pseudotyped with different reptarenavirus GPs to study the virus cell tropism. We found that scrVSV Delta G-eGFPs pseudotyped with reptarenavirus GPs readily entered mammalian cell lines, and some mammalian cell lines exhibited higher, compared to snake cell lines, susceptibility to reptarenavirus GP-mediated infection. Mammarenavirus GPs used as controls also mediated e fficient entry into several snake cell lines. Our results confirm an important role of the virus surface GP in reptarenavirus cell tropism and that mamma-and reptarenaviruses exhibit high cross-species transmission potential.