A Heterozygous STXBP1 Gene de novo Mutation in an Iranian Child With Epileptic Encephalopathy: Case Report
-
Masoud Heidari
,
Morteza Soleyman-Nejad
,
Mohammad Hossein Taskhiri
,
Alireza Isazadeh
,
Manzar Bolhassan
,
Javad Shahpouri
,
Mansour Heidari
,
Nahid Sadighi
Abstract
The Syntaxin Binding Protein 1 (STXBP1) plays an important role in regulating neurotransmitter release and synaptic vesicle fusion through binding to syntaxin-1A (STX1A) and changing its conformation. In this study, we identified a de novo mutation (c.C1162T: p.R388X) in exon 14 of the STXBP1 gene causing an epileptic encephalopathy, early infantile, non-epileptic movement, and unclassified infantile spasms disorders in a 5-year-old boy by whole-exome sequencing. The segregation of this genetic variant was examined in the patient as well as in his parents. We found the R388X in heterozygous state in the proband but not in his parents. This genetic change could be due to de nova mutation or germlinemosaicism.
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11. Ortega-Moreno L, Giraldez BG, Verdú A, Garcia-Campos O, Sánchez-Martín G, Serratosa JM, Guerrero-López R. Novel mutation in STXBP1 gene in a patient with non-lesional Ohtahara syndrome. Neurología (English Edition). 2016;31(8):523-7.
2. Barcia G, Chemaly N, Gobin S, Milh M, Van Bogaert P, Barnerias C, Kaminska A, Dulac O, Desguerre I, Cormier V, Boddaert N. Early epileptic encephalopathies associated with STXBP1 mutations: could we better delineate the phenotype? European journal of medical genetics. 2014;57(1):15-20.
3. Gerber SH, Rah JC, Min SW, Liu X, de Wit H, Dulubova I, Meyer AC, Rizo J, Arancillo M, Hammer RE, Verhage M. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science. 2008 Sep 12;321(5895):1507-10.
4. Carvill GL, Weckhuysen S, McMahon JM, Hartmann C, Møller RS, Hjalgrim H, Cook J, Geraghty E, O’Roak BJ, Petrou S, Clarke A. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology. 2014;82(14):1245-53.
5. Deprez L, Weckhuysen S, Holmgren P, Suls A, Van Dyck T, Goossens D, Del-Favero J, Jansen A, Verhaert K, Lagae L, Jordanova A. Clinical spectrum of early-onset epileptic encephalopathies associated with STXBP1 mutations. Neurology. 2010;75(13):1159-65.
6. Patzke C, Han Y, Covy J, Yi F, Maxeiner S, Wernig M, Südhof TC. Analysis of conditional heterozygous STXBP1 mutations in human neurons. The Journal of clinical investigation. 2015;125(9):3560-71.
7. Misura KM, Scheller RH, Weis WI. Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex. Nature. 2000;404(6776):355.
8. Stamberger H, Weckhuysen S, De Jonghe P. STXBP1 as a therapeutic target for epileptic encephalopathy. Expert opinion on therapeutic targets. 2017;21(11):1027-36.
9. Hamdan FF, Piton A, Gauthier J, Lortie A, Dubeau F, Dobrzeniecka S, Spiegelman D, Noreau A, Pellerin S, Côté M, Henrion E. De novo STXBP1 mutations in mental retardation and nonsyndromic epilepsy. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 2009;65(6):748-53.
10. Weimer RM, Richmond JE, Davis WS, Hadwiger G, Nonet ML, Jorgensen EM. Defects in synaptic vesicle docking in unc-18 mutants. Nature neuroscience. 2003;6(10):1023-30.
11. Ortega-Moreno L, Giraldez BG, Verdú A, Garcia-Campos O, Sánchez-Martín G, Serratosa JM, Guerrero-López R. Novel mutation in STXBP1 gene in a patient with non-lesional Ohtahara syndrome. Neurología (English Edition). 2016;31(8):523-7.
| Files | ||
| Issue | Vol 57, No 8 (2019) | |
| Section | Case Report(s) | |
| DOI | https://doi.org/10.18502/acta.v57i8.2429 | |
| Keywords | ||
| Syntaxin binding protein 1 (STXBP1) gene Mutation Epileptic encephalopathy | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Heidari M, Soleyman-Nejad M, Taskhiri MH, Isazadeh A, Bolhassan M, Shahpouri J, Heidari M, Sadighi N. A Heterozygous STXBP1 Gene de novo Mutation in an Iranian Child With Epileptic Encephalopathy: Case Report. Acta Med Iran. 2020;57(8):508-521.
