Clinical Evidence for Variegated Silencing in Patients With Friedreich Ataxia.
Journal
Neurology. Genetics
ISSN: 2376-7839
Titre abrégé: Neurol Genet
Pays: United States
ID NLM: 101671068
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
08
01
2022
accepted:
30
03
2022
entrez:
27
5
2022
pubmed:
28
5
2022
medline:
28
5
2022
Statut:
epublish
Résumé
Friedreich ataxia (FRDA) is a neurodegenerative disease caused by a GAA triplet repeat (GAA-TR) expansion in intron 1 of the The FRDA Clinical Outcome Measures Study database was used for a cross-sectional analysis of 1,000 patients with FRDA. Frataxin levels were determined by lateral flow immunoassays. The length of the GAA-TR in our cohort predicted frataxin level (R Our data suggest that there is a ceiling effect on the clinical consequences of GAA-TR length in FRDA, as would be predicted by variegated silencing. Patients with GAA-TRs of >700 triplets represent a subgroup in which the severity of clinical manifestations based on GAA-TR length have reached maximal levels and therefore display limited clinical variability in disease progression.
Sections du résumé
Background and Objectives
UNASSIGNED
Friedreich ataxia (FRDA) is a neurodegenerative disease caused by a GAA triplet repeat (GAA-TR) expansion in intron 1 of the
Methods
UNASSIGNED
The FRDA Clinical Outcome Measures Study database was used for a cross-sectional analysis of 1,000 patients with FRDA. Frataxin levels were determined by lateral flow immunoassays.
Results
UNASSIGNED
The length of the GAA-TR in our cohort predicted frataxin level (R
Discussion
UNASSIGNED
Our data suggest that there is a ceiling effect on the clinical consequences of GAA-TR length in FRDA, as would be predicted by variegated silencing. Patients with GAA-TRs of >700 triplets represent a subgroup in which the severity of clinical manifestations based on GAA-TR length have reached maximal levels and therefore display limited clinical variability in disease progression.
Identifiants
pubmed: 35620135
doi: 10.1212/NXG.0000000000000683
pii: NG2022017325
pmc: PMC9128033
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e683Informations de copyright
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Références
Front Neurosci. 2021 Nov 25;15:752921
pubmed: 34899161
Bioanalysis. 2015;7(15):1843-55
pubmed: 26295986
Ann Clin Transl Neurol. 2015 Aug;2(8):831-42
pubmed: 26339677
Mol Genet Metab. 2010 Oct-Nov;101(2-3):238-45
pubmed: 20675166
Lancet Neurol. 2016 Dec;15(13):1346-1354
pubmed: 27839651
Mol Genet Metab. 2007 Sep-Oct;92(1-2):23-35
pubmed: 17596984
Lancet Neurol. 2021 May;20(5):362-372
pubmed: 33770527
Neurology. 2006 Jun 13;66(11):1711-6
pubmed: 16769945
Hum Mol Genet. 2021 Feb 4;29(23):3818-3829
pubmed: 33432325
Neurology. 2018 Sep 4;91(10):e917-e930
pubmed: 30097477
Ann Clin Transl Neurol. 2021 Jun;8(6):1239-1250
pubmed: 33949801
EClinicalMedicine. 2020 Jan 08;18:100213
pubmed: 31938785
J Neurol Neurosurg Psychiatry. 2014 Sep;85(9):994-1002
pubmed: 24463479
Ann Clin Transl Neurol. 2016 Jul 25;3(9):684-94
pubmed: 27648458
J Neurol Sci. 2020 Mar 15;410:116642
pubmed: 31901720
J Neurol. 2013 Sep;260(9):2362-9
pubmed: 23775342
Lancet Neurol. 2015 Feb;14(2):174-82
pubmed: 25566998
Nature. 2003 Apr 24;422(6934):909-13
pubmed: 12712207
Sci Rep. 2018 Nov 19;8(1):17043
pubmed: 30451920
Neurol Genet. 2018 Jul 23;4(4):e250
pubmed: 30065952
Mov Disord. 2010 Mar 15;25(4):426-32
pubmed: 20063431
N Engl J Med. 1996 Oct 17;335(16):1169-75
pubmed: 8815938
Ann Neurol. 2021 Feb;89(2):212-225
pubmed: 33068037