Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Clinical Evaluation
3.2. Genetic Analysis
3.3. Electrophysiological Testing
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Bansagi, B.; Griffin, H.; Whittaker, R.G.; Antoniadi, T.; Evangelista, T.; Miller, J.; Greenslade, M.; Forester, N.; Duff, J.; Bradshaw, A.; et al. Genetic heterogeneity of motor neuropathies. Neurology 2017, 88, 1226–1234. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Rossor, A.M.; Kalmar, B.; Greensmith, L.; Reilly, M.M. The distal hereditary motor neuropathies. J. Neurol. Neurosurg. Psychiatr. 2011, 83, 6–14. [Google Scholar] [CrossRef] [PubMed]
- Herrmann, D.N.; Horvath, R.; Sowden, J.E.; Gonzales, M.; Whittaker, R.G.; Lane, M.; Pyle, A.; Griffin, H.; Lloyd, T.E.; Chinnery, P.F.; et al. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am. J. Hum. Genet. 2014, 95, 332–339. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Montes-Chinea, N.I.; Guan, Z.; Coutts, M.; Vidal, C.; Courel, S.; Rebelo, A.P.; Abreu, L.; Zuchner, S.; Littleton, J.T.; Saporta, M.A. Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype. Neurol. Genet. 2018, 4, e282. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Littleton, J.; Stern, M.; Schulze, K.; Perin, M.; Bellen, H.J. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca2+-activated neurotransmitter release. Cell 1993, 74, 1125–1134. [Google Scholar] [CrossRef]
- Whittaker, R.G.; Herrmann, D.N.; Bansagi, B.; Hasan, B.A.S.; Lofra, R.M.; Logigian, E.L.; Sowden, J.E.; Almodovar, J.L.; Littleton, J.T.; Zuchner, S.; et al. Electrophysiologic features ofSYT2mutations causing a treatable neuromuscular syndrome. Neurology 2015, 85, 1964–1971. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Niguidula, N.; Alamillo, C.; Chao, E.C.; Powis, Z.; Cohen, J.S.; Hagman, K.F. Clinical whole-exome sequencing results impact medical management. Mol. Genet. Genom. Med. 2018, 6, 1068–1078. [Google Scholar] [CrossRef] [PubMed]
- Schabhüttl, M.; Wieland, T.; Senderek, J.; Baets, J.; Timmerman, V.; De Jonghe, P.; Reilly, M.M.; Stieglbauer, K.; Laich, E.; Windhager, R.; et al. Whole-exome sequencing in patients with inherited neuropathies: Outcome and challenges. J. Neurol. 2014, 261, 970–982. [Google Scholar] [CrossRef]
- Richards, S.; Aziz, N.; Bale, S.; Bick, D.; Das, S.; Gastier-Foster, J.; Grody, W.W.; Hegde, M.; Lyon, E.; Spector, E.; et al. Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 2015, 17, 405–423. [Google Scholar] [CrossRef]
- Sutton, R.B.; Davletov, B.A.; Berghuis, A.M.; Sudhof, T.C.; Sprang, S.R. Structure of the first C2 domain of synaptotagmin I: A novel Ca2+/phospholipid-binding fold. Cell 1995, 80, 929–938. [Google Scholar] [CrossRef][Green Version]
- Mackler, J.M.; Drummond, J.A.; Loewen, C.A.; Robinson, I.M.; Reist, N.E. The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nat. Cell Biol. 2002, 418, 340–344. [Google Scholar] [CrossRef] [PubMed]
- Lee, J.; Guan, Z.; Akbergenova, Y.; Littleton, J.T. Genetic analysis of synaptotagmin C2 domain specificity in regulating spontaneous and evoked neurotransmitter release. J. Neurosci. 2013, 33, 187–200. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kalia, S.S.; Adelman, K.; Bale, S.J.; Chung, W.K.; Eng, C.; Evans, J.P.; Herman, G.E.; Hufnagel, S.B.; Klein, T.E.; Korf, B.R.; et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): A policy statement of the American College of Medical Genetics and Genomics. Genet. Med. 2016, 19, 249–255. [Google Scholar] [CrossRef] [PubMed][Green Version]
N | Frequency, Hz | Number of Incentives | Amplitude M-Response, mV | Decrement., % (1–5) | Decrement., % (1–last) | Area, mV × ms | Decrement of Area, % (1–last) |
---|---|---|---|---|---|---|---|
1 | 3.0 | 5 | 10.5 | 4.5 | 4.5 | 28.1 | 5.4 |
2 | 3.0 | 5 | 10.4 | 7.4 | 7.4 | 27.7 | 7.6 |
3 | 3.0 | 5 | 10.5 | 6.1 | 6.1 | 27.7 | 4.4 |
4 | 3.0 | 5 | 10.1 | 6.6 | 6.6 | 26.7 | 8.5 |
5 | 50.0 | 200 | 9.96 | 2.3 | +13.9 | 26.1 | 24.2 |
6 | 3.0 | 5 | 15.5 | 0.8 | 0.8 | 34.3 | +5.4 |
7 | 3.0 | 5 | 13.3 | 2.0 | 2.0 | 34.1 | 1.4 |
8 | 3.0 | 5 | 12.2 | 5.2 | 5.2 | 32.2 | 6.6 |
9 | 3.0 | 5 | 11.7 | 5.2 | 5.2 | 31.1 | 5.6 |
10 | 3.0 | 5 | 10.7 | 2.1 | 2.1 | 28.3 | 3.4 |
Duration of MUPs | ||||||
---|---|---|---|---|---|---|
Min. Dur., ms | Max. Dur., ms | Average Dur., ms | Norm., ms | Dur. Deviation, % | Stage | Number of MUPs |
6.52 | 12.7 | 9.19 | 9.2 | Norm | Norm | 29 |
Amplitude of MUPs | ||||||
Min. Amp, mkV | Max. Amp, mkV | Average Amp., mkV | Norm Amp., mkV | Amp. Deviation, % | Amp. > 1 mV, % | Polyphase MUPs, % |
194 | 517 | 355 | 475 | Norm | 0 | 5.8 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Mironovich, O.; Dadali, E.; Malmberg, S.; Markova, T.; Ryzhkova, O.; Poliakov, A. Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy. Genes 2020, 11, 1238. https://doi.org/10.3390/genes11111238
Mironovich O, Dadali E, Malmberg S, Markova T, Ryzhkova O, Poliakov A. Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy. Genes. 2020; 11(11):1238. https://doi.org/10.3390/genes11111238
Chicago/Turabian StyleMironovich, Olga, Elena Dadali, Sergey Malmberg, Tatyana Markova, Oxana Ryzhkova, and Aleksander Poliakov. 2020. "Identification of a Novel de Novo Variant in the SYT2 Gene Causing a Rare Type of Distal Hereditary Motor Neuropathy" Genes 11, no. 11: 1238. https://doi.org/10.3390/genes11111238