2024
Muscles

An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?

Authors:

Theresa Paulus, Natalie Young, Emily Jessop, Carolin Berwanger, Christoph Stephan Clemen, Rolf Schröder, Rafal Ploski, Christian Hagel, Yorck Hellenbroich, Andreas Moser, Iakowos Karakesisoglou

Keywords:

emerin; lamin A/C; laminopathies; LINC complex; myalgia; nesprin; nesprin-2 giant; nuclear shape; SYNE2

Abstract:

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.