Introduction: As with many genetic diseases, the diagnostic role of next-generation sequencing is invaluable for early-onset epileptic encephalopathies. SNARE proteins in synaptic vesicles (synaptobrevin-2) and synaptic plasma membrane (syntaxin-1, SNAP-25) are involved in synaptic exocytosis and recycling. Patient Presentation: Here, we report a patient that started in early childhood with seizures resistant to antiepileptic drugs, then developed epileptic encephalopathy. Discussion/Conclusion: The NAPB gene encodes proteins in the SNARE complex. A previously unidentified homozygous missense variant in the NAPB gene may have contributed significantly to the etiology of our patient with epileptic encephalopathy. We also summarize the clinical, radiological, laboratory, and genetic findings of previously published patients with NAPB variants.

1.
Berg
AT
,
Berkovic
SF
,
Brodie
MJ
,
Buchhalter
J
,
Cross
JH
,
van Emde Boas
W
, et al
.
Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009
.
Epilepsia
.
2010
;
51
(
4
):
676
85
.
2.
Scheffer
IE
,
Berkovic
S
,
Capovilla
G
,
Connolly
MB
,
French
J
,
Guilhoto
L
, et al
.
ILAE classification of the epilepsies: position paper of the ILAE commission for classification and terminology
.
Epilepsia
.
2017
;
58
(
4
):
512
21
.
3.
Specchio
N
,
Wirrell
EC
,
Scheffer
IE
,
Nabbout
R
,
Riney
K
,
Samia
P
, et al
.
International League against epilepsy classification and definition of epilepsy syndromes with onset in childhood: position paper by the ILAE task force on nosology and definitions
.
Epilepsia
.
2022
;
63
(
6
):
1398
442
.
4.
Gun-Bilgic
D
,
Aydin-Gumus
A
,
Bilgic
A
,
Cam
FS
.
Mutations of BRCA1/2 genes in the west of Turkey and genotype-phenotype correlations
.
Clin Lab
.
2022
;
68
(
01
).
5.
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
(
3
):
473
87
.
6.
Chang
LF
,
Chen
S
,
Liu
CC
,
Pan
X
,
Jiang
J
,
Bai
XC
, et al
.
Structural characterization of full-length NSF and 20S particles
.
Nat Struct Mol Biol
.
2012
;
19
(
3
):
268
75
.
7.
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
(
2
):
E1
3
.
8.
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 Psychiatry
.
2017
;
74
(
3
):
293
9
.
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
(
1
):
104101
.
10.
Ravix
C
,
Riccardi
F
,
Daquin
G
,
Cacciagli
P
,
Lamoureux-Toth
S
,
Villard
L
, et al
.
NAPB and developmental and epileptic encephalopathy: description of the electroclinical profile associated with a novel pathogenic variant
.
Epilepsia
.
2023
;
64
(
6
):
e127
34
.
11.
Howell
KB
,
Harvey
AS
,
Archer
JS
.
Epileptic encephalopathy: use and misuse of a clinically and conceptually important concept
.
Epilepsia
.
2016
;
57
(
3
):
343
7
.
12.
Wei
F
,
Yan
LM
,
Su
T
,
He
N
,
Lin
ZJ
,
Wang
J
, et al
.
Ion channel genes and epilepsy: functional alteration, pathogenic potential, and mechanism of epilepsy
.
Neurosci Bull
.
2017
;
33
(
4
):
455
77
.
13.
He
N
,
Lin
ZJ
,
Wang
J
,
Wei
F
,
Meng
H
,
Liu
XR
, et al
.
Evaluating the pathogenic potential of genes with de novo variants in epileptic encephalopathies
.
Genet Med
.
2019
;
21
(
1
):
17
27
.
14.
Xi
Z
,
Deng
W
,
Wang
L
,
Xiao
F
,
Li
J
,
Wang
Z
, et al
.
Association of alpha-soluble NSF attachment protein with epileptic seizure
.
J Mol Neurosci
.
2015
;
57
(
3
):
417
25
.
15.
Chaudhuri
T
,
Chintalapati
J
,
Hosur
MV
.
Identification of 3'-UTR single nucleotide variants and prediction of select protein imbalance in mesial temporal lobe epilepsy patients
.
PLoS One
.
2021
;
16
(
6
):
e0252475
.
You do not currently have access to this content.