Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.
NR4A2
developmental delay
dystonia
next generation sequencing
parkinsonism
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
16
07
2019
revised:
13
12
2019
accepted:
26
12
2019
pubmed:
11
1
2020
medline:
28
4
2021
entrez:
11
1
2020
Statut:
ppublish
Résumé
The group of dystonia genes is expanding, and mutations of these genes have been associated with various combined dystonia syndromes. Among the latter, the cause of some dystonia parkinsonism cases remains unknown. To report patients with early-onset dystonia parkinsonism as a result of loss-of-function mutations in nuclear receptor subfamily 4 group A member 2. Phenotypic characterization and exome sequencing were carried out in 2 families. The 2 patients reported here both had a history of mild intellectual disability in childhood and subsequently developed dystonia parkinsonism in early adulthood. Brain magnetic resonance imaging was normal, and DATscan suggested bilateral dopaminergic denervation. Two frameshift mutations in NR4A2 were identified: a de novo insertion (NM_006186.3; c.326dupA) in the first case and another small insertion (NM_006186.3; c.881dupA) in the second. NR4A2 haploinsufficiency mutations have been recently reported in neurodevelopmental phenotypes. Our findings indicate that dystonia and/or parkinsonism may appear years after initial symptoms. Mutations in NR4A2 should be considered in patients with unexplained dystonia parkinsonism. © 2020 International Parkinson and Movement Disorder Society.
Sections du résumé
BACKGROUND
The group of dystonia genes is expanding, and mutations of these genes have been associated with various combined dystonia syndromes. Among the latter, the cause of some dystonia parkinsonism cases remains unknown.
OBJECTIVE
To report patients with early-onset dystonia parkinsonism as a result of loss-of-function mutations in nuclear receptor subfamily 4 group A member 2.
METHODS
Phenotypic characterization and exome sequencing were carried out in 2 families.
RESULTS
The 2 patients reported here both had a history of mild intellectual disability in childhood and subsequently developed dystonia parkinsonism in early adulthood. Brain magnetic resonance imaging was normal, and DATscan suggested bilateral dopaminergic denervation. Two frameshift mutations in NR4A2 were identified: a de novo insertion (NM_006186.3; c.326dupA) in the first case and another small insertion (NM_006186.3; c.881dupA) in the second.
CONCLUSIONS
NR4A2 haploinsufficiency mutations have been recently reported in neurodevelopmental phenotypes. Our findings indicate that dystonia and/or parkinsonism may appear years after initial symptoms. Mutations in NR4A2 should be considered in patients with unexplained dystonia parkinsonism. © 2020 International Parkinson and Movement Disorder Society.
Substances chimiques
NR4A2 protein, human
0
Nuclear Receptor Subfamily 4, Group A, Member 2
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
880-885Subventions
Organisme : France Parkinson
Pays : International
Organisme : Revue Neurologique
Pays : International
Informations de copyright
© 2020 International Parkinson and Movement Disorder Society.
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