Novel deep intronic mutation in PLA2G6 causing early-onset Parkinson's disease with brain iron accumulation through pseudo-exon activation.
Deep intronic variant
Early-onset Parkinson’s disease
NBIA
PLA2G6
PLAN
Pseudo-exon activation
Journal
Neurogenetics
ISSN: 1364-6753
Titre abrégé: Neurogenetics
Pays: United States
ID NLM: 9709714
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
22
04
2021
accepted:
04
08
2021
pubmed:
14
8
2021
medline:
4
2
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
PLA2G6 is the causative gene for a group of autosomal recessive neurodegenerative disorders known as PLA2G6-associated neurodegeneration (PLAN). We present a case with early-onset parkinsonism, ataxia, cognitive decline, cerebellar atrophy, and brain iron accumulation. Sequencing of PLA2G6 coding regions identified only a heterozygous nonsense variant, but mRNA analysis revealed the presence of an aberrant transcript isoform due to a novel deep intronic variant (c.2035-274G > A) leading to activation of an intronic pseudo-exon. These results expand the genotypic spectrum of PLAN, showing the paramount importance of detecting possible pathogenic variants in deep intronic regions in undiagnosed patients.
Identifiants
pubmed: 34387792
doi: 10.1007/s10048-021-00667-0
pii: 10.1007/s10048-021-00667-0
pmc: PMC8426226
doi:
Substances chimiques
Group VI Phospholipases A2
EC 3.1.1.4
PLA2G6 protein, human
EC 3.1.1.4
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
347-351Informations de copyright
© 2021. The Author(s).
Références
Eur J Neurol. 2013 Feb;20(2):322-30
pubmed: 22934738
Mov Disord Clin Pract. 2016 Mar 31;4(1):125-128
pubmed: 30868093
Neurology. 2008 Oct 28;71(18):1402-9
pubmed: 18799783
Cell. 2019 Jan 24;176(3):535-548.e24
pubmed: 30661751
Clin Genet. 2010 Nov;78(5):432-40
pubmed: 20584031
Hum Genet. 2017 Sep;136(9):1093-1111
pubmed: 28497172
BMC Neurol. 2020 Mar 17;20(1):101
pubmed: 32183746
J Mol Diagn. 2021 Jun;23(6):732-741
pubmed: 33781964
PLoS One. 2016 May 19;11(5):e0155605
pubmed: 27196560
Eur J Paediatr Neurol. 2018 Mar;22(2):272-284
pubmed: 29409688
Ann Neurol. 2009 Jan;65(1):19-23
pubmed: 18570303
Nat Genet. 2006 Jul;38(7):752-4
pubmed: 16783378
Parkinsonism Relat Disord. 2019 Aug;65:159-164
pubmed: 31196701
Front Neurol. 2018 Dec 18;9:1100
pubmed: 30619057
Front Neurol. 2018 Jul 10;9:536
pubmed: 30042723