NAPB and developmental and epileptic encephalopathy: Description of the electroclinical profile associated with a novel pathogenic variant.
NAPB seizures
SNAP SNARE
developmental and epileptic encephalopathies
electroencephalogram
whole exome sequencing
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
revised:
30
03
2023
received:
10
11
2022
accepted:
31
03
2023
medline:
5
6
2023
pubmed:
5
4
2023
entrez:
4
4
2023
Statut:
ppublish
Résumé
Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. DEE are genetically heterogeneous, and the proteins involved play roles in multiple pathways such as synaptic transmission, metabolism, neuronal development or maturation, transcriptional regulation, and intracellular trafficking. We performed whole exome sequencing on a consanguineous family with three children presenting an early onset (<6 months) with clusters of seizures characterized by oculomotor and vegetative manifestations, with an occipital origin. Before 1 year of age, interictal electroencephalographic recordings were well organized and neurodevelopment was unremarkable. Then, a severe regression occurred. We identified a novel homozygous protein-truncating variant in the NAPB (N-ethylmaleimide-sensitive fusion [NSF] attachment protein beta) gene that encodes the βSNAP protein, a key regulator of NSF-adenosine triphosphatase. This enzyme is essential for synaptic transmission by disassembling and recycling proteins of the SNARE complex. Here, we describe the electroclinical profile of each patient during the disease course. Our findings strengthen the association between biallelic variants in NAPB and DEE and refine the associated phenotype. We suggest including this gene in the targeted epilepsy gene panels used for routine diagnosis of unexplained epilepsy.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e127-e134Informations de copyright
© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.
Références
Hebbar M, Mefford HC. Recent advances in epilepsy genomics and genetic testing. F1000Res. 2020;9:F1000 Faculty Rev-185.
Sudhof TC. The synaptic vesicle cycle. Annu Rev Neurosci. 2004;27:509-47.
Verhage M, Sørensen JB. SNAREopathies: diversity in mechanisms and symptoms. Neuron. 2020;107:22-37.
Conroy J, Allen NM, Gorman KM, Shahwan A, Ennis S, Lynch SA, et al. NAPB - a novel SNARE-associated protein for early-onset epileptic encephalopathy. Clin Genet. 2016;89:E1-3.
Reuter MS, Tawamie H, Buchert R, Hosny Gebril O, Froukh T, Thiel C, et al. Diagnostic yield and novel candidate genes by exome sequencing in 152 consanguineous families with neurodevelopmental disorders. JAMA Psychiat. 2017;74:293-9.
Zhao X, Wang Y, Cai A, Mei S, Liu N, Kong X. A novel NAPB splicing mutation identified by trio-based exome sequencing is associated with early-onset epileptic encephalopathy. Eur J Med Genet. 2021;64:104101.
Denis J, Villeneuve N, Cacciagli P, Mignon-Ravix C, Lacoste C, Lefranc J, et al. Clinical study of 19 patients with SCN8A-related epilepsy: two modes of onset regarding EEG and seizures. Epilepsia. 2019;60:845-56.
Kopanos C, Tsiolkas V, Kouris A, Chapple CE, Albarca Aguilera M, Meyer R, et al. VarSome: the human genomic variant search engine. Bioinformatics. 2019;35:1978-80.
Zuberi SM, Wirrell E, Yozawitz E, Wilmshurst JM, Specchio N, Riney K, et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: position statement by the ILAE task force on nosology and definitions. Epilepsia. 2022;63:1349-97.
Villeneuve N, Laguitton V, Viellard M, Lépine A, Chabrol B, Dravet C, et al. Cognitive and adaptive evaluation of 21 consecutive patients with Dravet syndrome. Epilepsy Behav. 2014;31:143-8.
Balagura G, Xian J, Riva A, Marchese F, Ben Zeev B, Rios L, et al. Epilepsy course and developmental trajectories in STXBP1-DEE. Neurol Genet. 2022;8:e676.
Di Meglio C, Lesca G, Villeneuve N, Lacoste C, Abidi A, Cacciagli P, et al. Epileptic patients with de novo STXBP1 mutations: key clinical features based on 24 cases. Epilepsia. 2015;56:1931-40.
Talwar D, Hammer MF. SCN8A epilepsy, developmental encephalopathy, and related disorders. Pediatr Neurol. 2021;122:76-83.
Burgalossi A, Jung S, Meyer G, Jockusch WJ, Jahn O, Taschenberger H, et al. SNARE protein recycling by αSNAP and βSNAP supports synaptic vesicle priming. Neuron. 2010;68:473-87.
Whiteheart SW, Griff IC, Brunner M, Clary DO, Mayer T, Buhrow SA, et al. SNAP family of NSF attachment proteins includes a brain-specific isoform. Nature. 1993;362:353-5.
Chae TH, Kim S, Marz KE, Hanson PI, Walsh CA. The hyh mutation uncovers roles for alpha Snap in apical protein localization and control of neural cell fate. Nat Genet. 2004;36:264-70.
Sudlow AW, McFerran BW, Bodill H, Barnard RJ, Morgan A, Burgoyne RD. Similar effects of alpha- and beta-SNAP on Ca(2+)-regulated exocytosis. FEBS Lett. 1996;393:185-8.
Ali G, Habbab W, Alkhadairi G, Al-Shaban FA, Stanton LW. Generation of induced pluripotent stem cell lines from nonaffected parents and monozygotic triplets affected with autism spectrum disorder and epilepsy. Stem Cell Res. 2022;65:102943.
Sheidley BR, Malinowski J, Bergner AL, Bier L, Gloss DS, Mu W, et al. Genetic testing for the epilepsies: a systematic review. Epilepsia. 2022;63:375-87.
Smith L, Malinowski J, Ceulemans S, Peck K, Walton N, Sheidley BR, et al. Genetic testing and counseling for the unexplained epilepsies: an evidence-based practice guideline of the National Society of genetic counselors. J Genet Couns. 2022; 32:266-80. https://doi.org/10.1002/jgc4.1646