Abstract
The Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with great clinical and genetic heterogeneity. Mutations in DNM2 have been associated with CMT dominant intermediate B (CMTDIB). However, mutations in the same gene are known to induce also axonal CMT (CMT2M) or centronuclear myopathy. Moreover, the ability of effectively and simultaneously sequencing different CMT-related genes by next-generation sequencing approach makes it possible to detect even the presence of modifier genes that sometimes give reason of clinical variability in the context of complex phenotypes. Here, we describe an Italian family with very variable severity of phenotype among members harboring a novel DNM2 gene mutation which caused a prevalent CMT2M phenotype. The contemporary presence of a de novo variant in PRX gene in the most severely affected family member suggests a possible modulator effect of the PRX variant thus highlighting the possible impact of modifier genes in CMT.
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The authors thank the Cell lines and DNA bank of the Rett syndrome, X-linked mental retardation, and other genetic diseases, members of the Telethon Network of Genetic Biobanks (project no. GTB18001), funded by Telethon Italy, and the EuroBioBank network, for financial support.
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Lopergolo, D., Bocci, S., Pinto, A.M. et al. A new mutation in DNM2 gene in a large Italian family. Neurol Sci 42, 2509–2513 (2021). https://doi.org/10.1007/s10072-020-04972-8
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DOI: https://doi.org/10.1007/s10072-020-04972-8