An Intronic Heterozygous <i>SYNE2</i> Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?
Theresa Paulus,
Natalie Young,
Emily Jessop,
Carolin Berwanger,
Christoph Stephan Clemen,
Rolf Schröder,
Rafal Ploski,
Christian Hagel,
Yorck Hellenbroich,
Andreas Moser,
Iakowos Karakesisoglou
Affiliations
Theresa Paulus
Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
Natalie Young
Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
Emily Jessop
Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
Carolin Berwanger
Institute of Aerospace Medicine, German Aerospace Center, Linder Höhe, 51147 Cologne, Germany
Christoph Stephan Clemen
Institute of Aerospace Medicine, German Aerospace Center, Linder Höhe, 51147 Cologne, Germany
Rolf Schröder
Institute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany
Rafal Ploski
Department of Medical Genetics, Medical University of Warsaw, Pawińskiego 3c, 02-106 Warsaw, Poland
Christian Hagel
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20251 Hamburg, Germany
Yorck Hellenbroich
Institute of Human Genetics, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
Andreas Moser
Department of Neurology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
Iakowos Karakesisoglou
Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK
SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T>G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia.
