Inherited RORB pathogenic variants: Overlap of photosensitive genetic generalized and occipital lobe epilepsy.
GGE
IPOE
intellectual disability
photosensitivity
retinoid-related orphan receptor β
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
19
11
2019
revised:
19
02
2020
accepted:
19
02
2020
pubmed:
13
3
2020
medline:
21
10
2020
entrez:
13
3
2020
Statut:
ppublish
Résumé
Variants in RORB have been reported in eight individuals with epilepsy, with phenotypes ranging from eyelid myoclonia with absence epilepsy to developmental and epileptic encephalopathies. We identified novel RORB variants in 11 affected individuals from four families. One was from whole genome sequencing and three were from RORB screening of three epilepsy cohorts: developmental and epileptic encephalopathies (n = 1021), overlap of generalized and occipital epilepsy (n = 84), and photosensitivity (n = 123). Following interviews and review of medical records, individuals' seizure and epilepsy syndromes were classified. Three novel missense variants and one exon 3 deletion were predicted to be pathogenic by in silico tools, not found in population databases, and located in key evolutionary conserved domains. Median age at seizure onset was 3.5 years (0.5-10 years). Generalized, predominantly absence and myoclonic, and occipital seizures were seen in all families, often within the same individual (6/11). All individuals with epilepsy were photosensitive, and seven of 11 had cognitive abnormalities. Electroencephalograms showed generalized spike and wave and/or polyspike and wave. Here we show a striking RORB phenotype of overlap of photosensitive generalized and occipital epilepsy in both individuals and families. This is the first report of a gene associated with this overlap of epilepsy syndromes.
Identifiants
pubmed: 32162308
doi: 10.1111/epi.16475
pmc: PMC7363501
mid: NIHMS1573631
doi:
Substances chimiques
Nuclear Receptor Subfamily 1, Group F, Member 2
0
RORB protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23-e29Subventions
Organisme : Cure Kids New Zealand
Pays : International
Organisme : NICHD NIH HHS
ID : P50 HD103524
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS069605
Pays : United States
Organisme : Health Research Council of New Zealand
Pays : International
Organisme : Victorian Government's Operational Infrastructure Support Program
Pays : International
Organisme : Ted and Mollie Carr Endowment Trust
Pays : International
Organisme : National Health and Medical Research Council
Pays : International
Informations de copyright
Wiley Periodicals, Inc. © 2020 International League Against Epilepsy.
Références
Eur J Hum Genet. 2016 Dec;24(12):1761-1770
pubmed: 27352968
Brain. 2004 Aug;127(Pt 8):1878-86
pubmed: 15201194
Mov Disord. 2012 Dec;27(14):1797-800
pubmed: 23124580
Nat Genet. 1993 Aug;4(4):398-403
pubmed: 8401589
Neurology. 2015 Jul 28;85(4):316-24
pubmed: 26115733
Brain. 2017 Aug 1;140(8):2144-2156
pubmed: 28899008
J Med Genet. 2016 Dec;53(12):850-858
pubmed: 27358180
Epilepsia. 2017 Apr;58(4):512-521
pubmed: 28276062
Eur J Med Genet. 2013 Mar;56(3):163-70
pubmed: 23279911
Neurology. 2013 Apr 2;80(14):1322-9
pubmed: 23486866
Nat Genet. 2013 Jul;45(7):825-30
pubmed: 23708187
Epilepsia. 1992 Nov-Dec;33(6):1065-71
pubmed: 1464265
EMBO J. 1998 Jul 15;17(14):3867-77
pubmed: 9670004
Genome Res. 2013 May;23(5):843-54
pubmed: 23382536
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17534-9
pubmed: 19805139
Int J Mol Med. 2015 Jun;35(6):1493-500
pubmed: 25816151
Am J Hum Genet. 2012 Jan 13;90(1):152-60
pubmed: 22243967
Curr Top Dev Biol. 2017;125:227-255
pubmed: 28527573