Abstract
We report a case of progressive myoclonic epilepsy caused by a novel mutation in EPM2A. The female patient experienced abnormal jerky movements of the involving all four limbs and several generalized seizures, degeneration of cognition, and unsteadiness. Genetic analysis identified two rare, deleterious mutations in exon4: chr6: 145,948,751(c.G797G > A) and chr6: 145,948,761(c.T787C > T). The mutations at these two loci were from the genomes of their mother and father, respectively, which were compound heterozygous variations. This report updates the mutation sites of gene EPM2A and extends genotype–phenotype correlations in Lafora disease.
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References
Minassian BA (2001) Lafora’s disease: towards a clinical, pathologic, and molecular synthesis. Pediatr Neurol 25(1):21–29
Shahwan A, Farrell M, Delanty N (2005) Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol 4(4):239–248
Nitschke F, Ahonen SJ, Nitschke S, Mitra S, Minassian BA (2018) Lafora disease - from pathogenesis to treatment strategies. Nat Rev Neurol 14(10):606–617
Pondrelli F, Muccioli L, Licchetta L, Mostacci B, Zenesini C, Tinuper P, Vignatelli L, Bisulli F (2021) Natural history of Lafora disease: a prognostic systematic review and individual participant data meta-analysis. Orphanet J Rare Dis 16(1):362
Riva A, Orsini A, Scala M, Taramasso V, Canafoglia L, d’Orsi G, Di Claudio MT, Avolio C, D’Aniello A, Elia M, Franceschetti S, Di Gennaro G, Bisulli F, Tinuper P, Tappatà M, Romeo A, Freri E, Marini C, Costa C, Sofia V, Ferlazzo E, Magaudda A, Veggiotti P, Gennaro E, Pistorio A, Minetti C, Bianchi A, Striano S, Michelucci R, Zara F, Minassian BA, Striano P (2021) Italian cohort of Lafora disease: clinical features, disease evolution, and genotype-phenotype correlations. J Neurol Sci 424:117409
Turnbull J, Tiberia E, Striano P, Genton P, Carpenter S, Ackerley CA (2016 Sep 1) Minassian BA (2016) Lafora disease. Epileptic Disord. 18(S2):38–62
Gentry MS, Guinovart JJ, Minassian BA, Roach PJ, Serratosa JM (2018) Lafora disease offers a unique window into neuronal glycogen metabolism. J Biol Chem 293(19):7117–7125
Nitschke F, Sullivan MA, Wang P, Zhao X, Chown EE, Perri AM, Israelian L, Juana-López L, Bovolenta P, Rodríguez de Córdoba S, Steup M, Minassian BA (2017) Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease. EMBO Mol Med 9(7):906–917
Sullivan MA, Nitschke S, Steup M, Minassian BA (2017) Nitschke F (2017) Pathogenesis of Lafora disease: transition of soluble glycogen to insoluble polyglucosan. Int J Mol Sci. 18(8):1743
Raththagala M, Brewer MK, Parker MW, Sherwood AR, Wong BK, Hsu S, Bridges TM, Paasch BC, Hellman LM, Husodo S, Meekins DA, Taylor AO, Turner BD, Auger KD, Dukhande VV, Chakravarthy S, Sanz P, Woods VL Jr, Li S, Vander Kooi CW, Gentry MS (2015) Structural mechanism of laforin function in glycogen dephosphorylation and Lafora disease. Mol Cell 57(2):261–72
Kecmanović M, Keckarević-Marković M, Keckarević D, Stevanović G, Jović N, Romac S (2016) Genetics of Lafora progressive myoclonic epilepsy: current perspectives. Appl Clin Genet 9:49–53
Bhat S, Ganesh S (2018) New discoveries in progressive myoclonus epilepsies: a clinical outlook. Expert Rev Neurother 18(8):649–667
Singh S, Ganesh S (2009) Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes. Hum Mutat 30(5):715–723
Orsini A, Valetto A, Bertini V, Esposito M, Carli N, Minassian BA, Bonuccelli A, Peroni D, Michelucci R, Striano P (2019) The best evidence for progressive myoclonic epilepsy: a pathway to precision therapy. Seizure 71:247–257
Garcia-Gimeno MA, Rodilla-Ramirez PN, Viana R, Salas-Puig X, Brewer MK, Gentry MS, Sanz P (2018) A novel EPM2A mutation yields a slow progression form of Lafora disease. Epilepsy Res 145:169–177
Gómez-Abad C, Gómez-Garre P, Gutiérrez-Delicado E, Saygi S, Michelucci R, Tassinari CA, Rodríguez de Córdoba S, Serratosa JM (2005) Lafora disease due to EPM2B mutations: a clinical and genetic study. Neurology 64(6):982–986
Singh S, Sethi I, Francheschetti S, Riggio C, Avanzini G, Yamakawa K, Delgado-Escueta AV, Ganesh S (2006) Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora’s progressive myoclonic epilepsy. J Med Genet 43(9):e48
Cardinali S, Canafoglia L, Bertoli S, Franceschetti S, Lanzi G, Tagliabue A, Veggiotti P (2006) A pilot study of a ketogenic diet in patients with Lafora body disease. Epilepsy Res 69(2):129–134
Lesca G, Boutry-Kryza N, de Toffol B, Milh M, Steschenko D, Lemesle-Martin M, Maillard L, Foletti G, Rudolf G, Nielsen JE, áRogvi-Hansen B, Erdal J, Mancini J, Thauvin-Robinet C, M’Rrabet A, Ville D, Szepetowski P, Raffo E, Hirsch E, Ryvlin P, Calender A, Genton P (2010) Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease. Epilepsia 51(9):1691–8
Brewer MK, Uittenbogaard A, Austin GL, Segvich DM, DePaoli-Roach A, Roach PJ, McCarthy JJ, Simmons ZR, Brandon JA, Zhou Z, Zeller J, Young LEA, Sun RC, Pauly JR, Aziz NM, Hodges BL, McKnight TR, Armstrong DD, Gentry MS (2019) Targeting pathogenic Lafora bodies in Lafora disease using an antibody-enzyme fusion. Cell Metab 30(4):689-705.e6
Mikati MA, Tabbara F (2017) Managing Lafora body disease with vagal nerve stimulation. Epileptic Disord Int Epilepsy J Videotape 19(1):82–86
Acknowledgements
We would like to acknowledge the patient for generously permitting the use of the data in this report. The funding sources had no role in data analysis or interpretation, paper writing, or deciding to submit this paper for publication.
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The author’s research was supported by Guizhou Administration of Traditional Chinese Medicine (No.: QZYY-2021–006).
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The Medical Ethics Committees of the Institute of Affiliated Hospital of Zunyi Medical University approved this case report. Written informed consent was obtained from the patient for the publication of the present case report.
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Liang, T., Wu, J., Chen, H. et al. Novel mutation of EPM2A causes progressive myoclonic epilepsy: a case report. Neurol Sci 43, 3467–3471 (2022). https://doi.org/10.1007/s10072-022-05986-0
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DOI: https://doi.org/10.1007/s10072-022-05986-0