De Novo Truncating Variants in the Last Exon of SEMA6B Cause Progressive Myoclonic Epilepsy.
Adolescent
Adult
Alleles
Animals
Exome
/ genetics
Exons
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
Genetic Variation
/ genetics
Heterozygote
Humans
Male
Myoclonic Epilepsies, Progressive
/ genetics
Nonsense Mediated mRNA Decay
/ genetics
Seizures
/ genetics
Semaphorins
/ genetics
Young Adult
Zebrafish
/ genetics
CRISPR-Cas9
SEMA6B
developmental and epileptic encephalopathy (DEE)
genome editing
nonsense-mediated mRNA decay (NMD)
progressive myoclonic epilepsy
semaphorin
zebrafish
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
02 04 2020
02 04 2020
Historique:
received:
20
11
2019
accepted:
19
02
2020
pubmed:
15
3
2020
medline:
12
5
2020
entrez:
15
3
2020
Statut:
ppublish
Résumé
De novo variants (DNVs) cause many genetic diseases. When DNVs are examined in the whole coding regions of genes in next-generation sequencing analyses, pathogenic DNVs often cluster in a specific region. One such region is the last exon and the last 50 bp of the penultimate exon, where truncating DNVs cause escape from nonsense-mediated mRNA decay [NMD(-) region]. Such variants can have dominant-negative or gain-of-function effects. Here, we first developed a resource of rates of truncating DNVs in NMD(-) regions under the null model of DNVs. Utilizing this resource, we performed enrichment analysis of truncating DNVs in NMD(-) regions in 346 developmental and epileptic encephalopathy (DEE) trios. We observed statistically significant enrichment of truncating DNVs in semaphorin 6B (SEMA6B) (p value: 2.8 × 10
Identifiants
pubmed: 32169168
pii: S0002-9297(20)30053-7
doi: 10.1016/j.ajhg.2020.02.011
pmc: PMC7118575
pii:
doi:
Substances chimiques
SEMA6B protein, human
0
Semaphorins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
549-558Informations de copyright
Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Références
Development. 2014 Oct;141(19):3709-20
pubmed: 25209245
Nat Genet. 2014 Sep;46(9):944-50
pubmed: 25086666
Nature. 2007 Jan 11;445(7124):168-76
pubmed: 17151600
Cell. 2018 Aug 9;174(4):999-1014.e22
pubmed: 30096314
Nucleic Acids Res. 2009 Jan;37(Database issue):D211-5
pubmed: 18940856
J Hum Genet. 2018 Dec;63(12):1223-1229
pubmed: 30258207
Gene Expr Patterns. 2012 Mar-Apr;12(3-4):117-22
pubmed: 22330030
Nat Neurosci. 2002 Dec;5(12):1294-301
pubmed: 12436113
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
Nature. 2017 Feb 23;542(7642):433-438
pubmed: 28135719
Nature. 2018 Mar 29;555(7698):611-616
pubmed: 29562236
Genome Res. 2019 Feb;29(2):159-170
pubmed: 30587507
Nat Genet. 2019 Jan;51(1):88-95
pubmed: 30531870
Sci Rep. 2018 Jan 30;8(1):1845
pubmed: 29382872
Neuron. 2012 Nov 21;76(4):721-34
pubmed: 23177958
Neurosci Lett. 2017 Feb 22;641:70-76
pubmed: 28109776
Front Synaptic Neurosci. 2018 Apr 26;10:6
pubmed: 29760657
Nat Genet. 2019 Jan;51(1):106-116
pubmed: 30559488
Science. 2018 Apr 13;360(6385):176-182
pubmed: 29545511
Neuron. 2007 Jan 18;53(2):217-32
pubmed: 17224404
Mov Disord. 2011 Jul;26(8):1509-14
pubmed: 21506164
PLoS One. 2016 Jul 08;11(7):e0158686
pubmed: 27392094
Am J Hum Genet. 2017 Apr 6;100(4):650-658
pubmed: 28343630
PLoS One. 2013;8(1):e54166
pubmed: 23342097
Nat Cell Biol. 2004 Dec;6(12):1204-11
pubmed: 15543137
Neuroscience. 2005;131(3):759-68
pubmed: 15730879
Nature. 2015 Mar 12;519(7542):223-8
pubmed: 25533962
Curr Opin Neurobiol. 2009 Jun;19(3):263-74
pubmed: 19541473
Philos Trans A Math Phys Eng Sci. 2015 Mar 6;373(2036):
pubmed: 25624520
Semin Pediatr Neurol. 2019 Dec;32:100770
pubmed: 31813518
Am J Hum Genet. 2015 Apr 2;96(4):612-22
pubmed: 25817016
Cell. 2007 Jan 26;128(2):399-410
pubmed: 17254975
Semin Neurol. 2015 Jun;35(3):293-9
pubmed: 26060909
Brain. 1985 Mar;108 ( Pt 1):225-40
pubmed: 3919884
Cell Mol Life Sci. 2016 Apr;73(8):1609-22
pubmed: 26794845