Characterization of the phenotype with cognitive impairment and protein mislocalization in SCA34.
Journal
Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
26
09
2019
accepted:
21
01
2020
entrez:
27
3
2020
pubmed:
27
3
2020
medline:
27
3
2020
Statut:
epublish
Résumé
To better characterize the neurologic and cognitive profile of patients with spinocerebellar ataxia 34 (SCA34) caused by We investigated a 5-generation French-Canadian kindred presenting with a late-onset cerebellar ataxia and recruited age- and education-matched controls to evaluate the presence of neurocognitive impairment. Immunohistochemistry of dermal fibroblasts derived from a patient's skin biopsy was performed. Patients had a late-onset slowly progressive cerebellar syndrome (mean age at onset 47 years; range 32-60 years) characterized by truncal and limb ataxia, dysarthria, hypometric saccades, and saccadic pursuits. No patient had past or current signs of erythrokeratodermia variabilis, which had previously been reported. MRI revealed cerebellar atrophy, with pontine atrophy (4 of 6 patients), and cruciform hypersignal in the pons (2 of 6 patients). Fluorodeoxyglucose-PET showed diffuse cerebellar hypometabolism in all 5 tested patients with subtle parietal hypometabolism in 3. Significant cognitive deficits were found in executive functioning, along with apparent visuospatial, attention, and psychiatric involvement. Immunohistochemistry of dermal fibroblasts showed mislocalization of the ELOVL4 protein, which appeared punctate and aggregated, supporting a dominant negative effect of the mutation on protein localization. Our findings support the pathogenicity of
Identifiants
pubmed: 32211516
doi: 10.1212/NXG.0000000000000403
pii: NG2019012070
pmc: PMC7073455
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e403Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
JAMA Neurol. 2015 Jul;72(7):797-805
pubmed: 26010696
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
J Neurol Sci. 2018 Apr 15;387:70-74
pubmed: 29571875
Nat Methods. 2010 Apr;7(4):248-9
pubmed: 20354512
Acta Neuropathol Commun. 2015 Jan 31;3:5
pubmed: 25637145
Brain. 2014 Sep;137(Pt 9):2408-22
pubmed: 24871646
Cerebellum. 2010 Sep;9(3):443-53
pubmed: 20559786
Brain. 2017 Mar 1;140(3):707-720
pubmed: 28043955
Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4422-31
pubmed: 20393115
Cortex. 2010 Jul-Aug;46(7):831-44
pubmed: 20152963
J Biol Chem. 2005 Sep 16;280(37):32521-30
pubmed: 16036915
Front Neuroanat. 2017 May 01;11:38
pubmed: 28507511
Arch Dermatol. 1972 Aug;106(2):183-8
pubmed: 5048218
Genome Res. 2010 Sep;20(9):1297-303
pubmed: 20644199
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5446-51
pubmed: 23509295
Adv Exp Med Biol. 2016;854:129-35
pubmed: 26427403
Neurol Genet. 2018 Jul 26;4(4):e263
pubmed: 30065956
Neuroimage. 2012 Jan 16;59(2):1560-70
pubmed: 21907811
J Neurol. 2013 Dec;260(12):3134-43
pubmed: 24122064
Brain. 1998 Apr;121 ( Pt 4):561-79
pubmed: 9577385
Cerebellum Ataxias. 2015 Feb 27;2:2
pubmed: 26331045
Mov Disord. 2013 Aug;28(9):1200-8
pubmed: 23775899
J Am Geriatr Soc. 2005 Apr;53(4):695-9
pubmed: 15817019
JAMA Neurol. 2015 Aug;72(8):942-3
pubmed: 26258735
JAMA Neurol. 2014 Apr;71(4):470-5
pubmed: 24566826
Invest Ophthalmol Vis Sci. 2004 Dec;45(12):4263-7
pubmed: 15557430
Bioinformatics. 2010 Nov 15;26(22):2867-73
pubmed: 20926424
Mov Disord. 2018 Jul;33(7):1056-1076
pubmed: 29756227
J Cogn Neurosci. 2010 Nov;22(11):2663-76
pubmed: 19925191