DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability
- PMID: 23211418
- DOI: 10.1016/j.parkreldis.2012.11.006
DNAJC6 is responsible for juvenile parkinsonism with phenotypic variability
Abstract
Familial parkinson's disease is both clinically and genetically heterogeneous. By mapping the disease locus with a lod score of 5.13 to a < 3.5 Mbp region at 1p31.3 in a consanguineous family and subsequent exome sequencing analysis, we identified homozygous truncating mutation p.Q734X in DNAJC6. Four members of the family were afflicted with juvenile parkinsonism that presented with mental retardation, pyramidal signs and epilepsy, as well as varying degrees of a progressive neurological disease. Recently a splicing mutation in the same gene was reported in two brothers with juvenile parkinsonism that was not L-Dopa responsive and not accompanied by pyramidal signs or mental retardation. Also, an 80-kb deletion that included DNAJC6 sequences was identified in a boy reported as having obesity, epilepsy and mental retardation but not any signs of parkinsonism. The phenotype of our study family resembles both of those families, which among themselves do not share any clinical features. Our findings further establish DNAJC6 as a juvenile parkinsonism gene, and expand the spectrums of the parkinsonism phenotype and DNAJC6 mutation. DNAJC6 encodes the neuronal co-chaperone auxilin. We found that its transcript is highly significantly more abundant in brain as compared to the non-neural tissues assayed.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Similar articles
-
DNAJC6 Mutations Associated With Early-Onset Parkinson's Disease.Ann Neurol. 2016 Feb;79(2):244-56. doi: 10.1002/ana.24553. Epub 2016 Jan 14. Ann Neurol. 2016. PMID: 26528954
-
DNAJC6 Mutations Disrupt Dopamine Homeostasis in Juvenile Parkinsonism-Dystonia.Mov Disord. 2020 Aug;35(8):1357-1368. doi: 10.1002/mds.28063. Epub 2020 May 30. Mov Disord. 2020. PMID: 32472658 Free PMC article.
-
A deleterious mutation in DNAJC6 encoding the neuronal-specific clathrin-uncoating co-chaperone auxilin, is associated with juvenile parkinsonism.PLoS One. 2012;7(5):e36458. doi: 10.1371/journal.pone.0036458. Epub 2012 May 1. PLoS One. 2012. PMID: 22563501 Free PMC article.
-
DNAJC proteins and pathways to parkinsonism.FEBS J. 2019 Aug;286(16):3080-3094. doi: 10.1111/febs.14936. Epub 2019 Jun 20. FEBS J. 2019. PMID: 31120186 Free PMC article. Review.
-
Autosomal dominant parkinsonism: its etiologies and differential diagnoses.Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S1-3. doi: 10.1016/S1353-8020(11)70003-7. Parkinsonism Relat Disord. 2012. PMID: 22166400 Review.
Cited by
-
Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.Brain. 2024 Jun 3;147(6):2023-2037. doi: 10.1093/brain/awae020. Brain. 2024. PMID: 38242634 Free PMC article.
-
A Next-Generation Sequencing Study in a Cohort of Sicilian Patients with Parkinson's Disease.Biomedicines. 2023 Nov 22;11(12):3118. doi: 10.3390/biomedicines11123118. Biomedicines. 2023. PMID: 38137339 Free PMC article.
-
Pain in monogenic Parkinson's disease: a comprehensive review.Front Neurol. 2023 Oct 30;14:1248828. doi: 10.3389/fneur.2023.1248828. eCollection 2023. Front Neurol. 2023. PMID: 38020640 Free PMC article. Review.
-
Impaired pre-synaptic plasticity and visual responses in auxilin-knockout mice.iScience. 2023 Sep 6;26(10):107842. doi: 10.1016/j.isci.2023.107842. eCollection 2023 Oct 20. iScience. 2023. PMID: 37766983 Free PMC article.
-
Leveraging genetic diversity to understand monogenic Parkinson's disease's landscape in AfrAbia.Am J Neurodegener Dis. 2023 Aug 15;12(4):108-122. eCollection 2023. Am J Neurodegener Dis. 2023. PMID: 37736165 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous