Recurrent NUS1 canonical splice donor site mutation in two unrelated individuals with epilepsy, myoclonus, ataxia and scoliosis - a case report.
Epilepsy
NUS1
Whole-exome sequencing
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
27 Oct 2019
27 Oct 2019
Historique:
received:
28
05
2019
accepted:
02
10
2019
entrez:
29
10
2019
pubmed:
28
10
2019
medline:
10
1
2020
Statut:
epublish
Résumé
We encountered two unrelated individuals suffering from neurological disorders, including epilepsy and scoliosis. Whole-exome sequencing identified the same recurrent, de novo, pathogenic variant in NUS1 [NM_138459.4:c.691 + 1C > A] in both individuals. This variant is located in the conserved cis-prenyltransferase domain of the nuclear undecaprenyl pyrophosphate synthase 1 gene (NUS1), which encodes the Nogo-B receptor, an essential catalyst for protein glycosylation. This variant was confirmed to create a new splice donor site, resulting in aberrant RNA splicing resulting in a 91-bp deletion in exon 3 in both individuals. The mutant mRNA was partially degraded by nonsense mediated mRNA decay. To date, only four de novo variants and one homozygous variant have been reported in NUS1, which cause developmental and epileptic encephalopathy, early onset Parkinson's disease, and a congenital disorder of glycosylation. Seven patients, including our two patients, have presented with epileptic seizures and intellectual disabilities. Our study strongly supports the finding that this recurrent, de novo, variant in NUS1 causes developmental and epileptic encephalopathy with involuntary movement, ataxia and scoliosis.
Sections du résumé
BACKGROUND
BACKGROUND
We encountered two unrelated individuals suffering from neurological disorders, including epilepsy and scoliosis.
CASE PRESENTATION
METHODS
Whole-exome sequencing identified the same recurrent, de novo, pathogenic variant in NUS1 [NM_138459.4:c.691 + 1C > A] in both individuals. This variant is located in the conserved cis-prenyltransferase domain of the nuclear undecaprenyl pyrophosphate synthase 1 gene (NUS1), which encodes the Nogo-B receptor, an essential catalyst for protein glycosylation. This variant was confirmed to create a new splice donor site, resulting in aberrant RNA splicing resulting in a 91-bp deletion in exon 3 in both individuals. The mutant mRNA was partially degraded by nonsense mediated mRNA decay. To date, only four de novo variants and one homozygous variant have been reported in NUS1, which cause developmental and epileptic encephalopathy, early onset Parkinson's disease, and a congenital disorder of glycosylation. Seven patients, including our two patients, have presented with epileptic seizures and intellectual disabilities.
CONCLUSIONS
CONCLUSIONS
Our study strongly supports the finding that this recurrent, de novo, variant in NUS1 causes developmental and epileptic encephalopathy with involuntary movement, ataxia and scoliosis.
Identifiants
pubmed: 31656175
doi: 10.1186/s12883-019-1489-x
pii: 10.1186/s12883-019-1489-x
pmc: PMC6815447
doi:
Substances chimiques
NUS1 protein, human
0
RNA Splice Sites
0
Receptors, Cell Surface
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
253Subventions
Organisme : AMED
ID : JP18ek0109280
Organisme : AMED
ID : JP18dm0107090
Organisme : AMED
ID : JP18ek0109301
Organisme : AMED
ID : JP18ek0109348
Organisme : AMED
ID : JP18kk020500
Organisme : JSPS KAKENHI
ID : JP17H01539
Organisme : JSPS KAKENHI
ID : JP17K16132
Organisme : JSPS KAKENHI
ID : JP16H05357
Organisme : JSPS KAKENHI
ID : JP16H06254
Organisme : JSPS KAKENHI
ID : JP17K10080
Organisme : JSPS KAKENHI
ID : JP17K15630
Références
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11567-11572
pubmed: 30348779
Nat Genet. 2016 Oct;48(10):1112-8
pubmed: 27618451
Eur J Hum Genet. 2015 Feb;23(2):173-9
pubmed: 24824130
Am J Hum Genet. 2017 Nov 2;101(5):664-685
pubmed: 29100083
J Biol Chem. 2017 Oct 20;292(42):17351-17361
pubmed: 28842490
Cell Metab. 2014 Sep 2;20(3):448-57
pubmed: 25066056
Nature. 2016 Aug 17;536(7616):285-91
pubmed: 27535533
EMBO J. 2011 May 13;30(12):2490-500
pubmed: 21572394
J Comput Biol. 1997 Fall;4(3):311-23
pubmed: 9278062
Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10997-1002
pubmed: 16835300
Congenit Anom (Kyoto). 2016 Jul;56(4):187-189
pubmed: 27038333
Orphanet J Rare Dis. 2016 Jun 24;11(1):84
pubmed: 27343064
Biochem Biophys Res Commun. 2003 Dec 26;312(4):1349-56
pubmed: 14652022