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., …Karakesisoglou, I. (in press). 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
• Deposit Date: May 23, 2024
• Publicly Available Date: May 23, 2024
• Journal: Muscles
• 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