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

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

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.

Citation

Paulus, T., Young, N., Jessop, E., Berwanger, C., Clemen, C. S., Schröder, R., Ploski, R., Hagel, C., Hellenbroich, Y., Moser, A., & Karakesisoglou, I. (2024). An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?. Muscles, 3(1), 100-109. https://doi.org/10.3390/muscles3010010

• Journal Article Type: Article
• Acceptance Date: Mar 12, 2024
• Online Publication Date: Mar 15, 2024
• Publication Date: 2024-03
• Deposit Date: May 23, 2024
• Publicly Available Date: May 23, 2024
• Journal: Muscles
• Electronic ISSN: 2813-0413
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 3
• Issue: 1
• Pages: 100-109
• DOI: https://doi.org/10.3390/muscles3010010
• Keywords: LINC complex, lamin A/C, SYNE2, nesprin-2 giant, nuclear shape, emerin, laminopathies, nesprin, myalgia
• Public URL: https://durham-repository.worktribe.com/output/2379125