Abstract
Mutations in SEPN1 cause selenoprotein N (SEPN)-related myopathy (SEPN-RM) characterized by early-onset axial and neck weakness, spinal rigidity, respiratory failure and histopathological features, ranging from mild dystrophic signs to a congenital myopathy pattern with myofibrillar disorganization. We report on clinical and instrumental features in three patients affected with a congenital myopathy characterized by prevalent neck weakness starting at different ages and mild myopathy, in whom we performed diagnosis of SEPN-RM. The patients presented myopathic signs since their first years of life, but the disease remained unrecognized because of a relatively benign myopathic course. In two cases, myopathic features were stable after 2 years of follow-up, but respiratory involvement worsened. The muscle MRI and muscle biopsy showed a typical pattern of SEPN-RM. Molecular diagnosis revealed two novel homozygous mutations in SEPN1, c.1176delA and c.726_727InsTCC.
Conclusion: This report underlines the clinical diagnostic clues of early neck and axial weakness to suspect a SEPN-RM and the usefulness of muscle MRI in conjunction with clinical features to achieve the diagnosis. Our data confirm the slow progression of respiratory involvement in spite of the relatively stable course of myopathy. We report two previously undescribed mutations in SEPN1.
What is known: • Mutations in SEPN1 cause myopathy characterized by early-onset axial and neck weakness spinal rigidity and respiratory failure. • SEPN-related myopathies have been initially associated with four distinct histopathological entities that however appear more mixed in recently described cases. |
What is New: • SEPN-related myopathies can remain unrecognized because of the normal early motor development and relatively benign myopathic course of the disease. • Our study adds two novel homozygous mutations to the number of reported pathogenic SEPN1 variants. |
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Abbreviations
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- CK:
-
Creatine kinase
- LDH:
-
Lactate dehydrogenase
- MRI:
-
Magnetic resonance imaging
- NADH:
-
Dihydronicotinamide adenine dinucleotide dehydrogenase
- SEPN-RM:
-
SEPN-related myopathy
- VC:
-
Vital capacity
- WISC-R:
-
Wechsler Intelligence Scale for Children-Revised
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The study was supported by the Italian Telethon (grants no. GUP 11001 “Development of a registry and a database for a nation-wide Italian collaborative network on congenital muscular dystrophy” to IM). The EuroBioBank and Telethon Network of Genetic Biobanks (GTB12001F to MM) are gratefully acknowledged for providing the biological samples.
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The authors declare that they have no competing interests.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Parental written informed consent was obtained for muscle biopsy, genetic analysis and any images in the paper. A copy of the written consent is available for review by the Editor of this journal.
Authors’ contributions
AA, CB, MM and IM conceived and designed the experiments and wrote the manuscript. CB carried out the molecular analysis. FB and FS performed the immunochemical evaluation of muscle biopsies and prepared the figures. EM performed muscle MRI. LM performed muscle biopsy and histological evaluation and critically revised the manuscript. AA, CG and IM performed clinical studies. All authors read and approved the final manuscript.
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Communicated by Mario Bianchetti
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Ardissone, A., Bragato, C., Blasevich, F. et al. SEPN1-related myopathy in three patients: novel mutations and diagnostic clues. Eur J Pediatr 175, 1113–1118 (2016). https://doi.org/10.1007/s00431-015-2685-3
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DOI: https://doi.org/10.1007/s00431-015-2685-3