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Novel MTMR2 mutation causing severe Charcot-Marie-Tooth type 4B1 disease: a case report

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Abstract

Mutations in myotubularin-related protein 2 (MTMR2) were shown to underlie Charcot-Marie-Tooth type 4B1 (CMT4B1) disease, a rare autosomal recessive demyelinating neuropathy, characterized by severe early-onset motor and sensory neuropathy. We describe three siblings of consanguineous kindred presenting with hypotonia, reduced muscle tone, action tremor, dysmetria, areflexia, and skeletal deformities, consistent with a diagnosis of CMT. Whole-exome sequencing identified a novel homozygous c.336_337 insertion mutation in MTMR2, resulting in a frameshift and putative truncated protein. In this concise report, we discuss the clinical presentation of this rare disease and support the limited number of observations regarding the pathogenesis of MTMR2-related neuropathies.

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Acknowledgments

We thank the families for participating in this study.

Availability of data and materials

The data are available on request from the corresponding author.

Funding

The study was supported by the Legacy Heritage Bio-Medical program of the Israel Science Foundation (grant no. 1798/16), the Morris Kahn Family Foundation, and the National Knowledge Center for Rare / Orphan Diseases sponsored by the Israel Ministry of Science, Technology and Space.

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Authors and Affiliations

  1. The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Daniel Halperin, Aviad Sapir, Ohad Wormser, Max Drabkin, Yuval Yogev, Vadim Dolgin & Ohad S. Birk

  2. Zusman Child Development Center, Division of Pediatrics, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Hagit Flusser

  3. Genetics Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel

    Ohad S. Birk

Authors
  1. Daniel Halperin
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  2. Aviad Sapir
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  3. Ohad Wormser
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  4. Max Drabkin
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  5. Yuval Yogev
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  6. Vadim Dolgin
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  7. Hagit Flusser
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  8. Ohad S. Birk
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Contributions

Genetic and molecular studies: DH, AS, OW, MD, VD and YY. Clinical characterization: DH and HF. Writing the manuscript: DH, AS, and OSB. OSB initiated and supervised the project. Approved by all authors.

Corresponding author

Correspondence to Ohad S. Birk.

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Halperin, D., Sapir, A., Wormser, O. et al. Novel MTMR2 mutation causing severe Charcot-Marie-Tooth type 4B1 disease: a case report. Neurogenetics 21, 301–304 (2020). https://doi.org/10.1007/s10048-020-00617-2

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  • DOI: https://doi.org/10.1007/s10048-020-00617-2

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