ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia.
Alleles
Animals
Behavior, Animal
Cell Line
Crosses, Genetic
Disease Models, Animal
Dysautonomia, Familial
/ genetics
Exons
Fibroblasts
Genotype
Humans
Introns
Kinetin
/ genetics
Male
Mice
Mice, Inbred C57BL
Mutation
Neurons
/ metabolism
Phenotype
Proprioception
RNA Splicing
Transcriptional Elongation Factors
/ genetics
ELP1
IKAP
familial dysautonomia
neurodegenerative disease
splicing
therapeutics
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
04 04 2019
04 04 2019
Historique:
received:
08
10
2018
accepted:
08
02
2019
pubmed:
25
3
2019
medline:
6
2
2020
entrez:
26
3
2019
Statut:
ppublish
Résumé
Familial dysautonomia (FD) is a recessive neurodegenerative disease caused by a splice mutation in Elongator complex protein 1 (ELP1, also known as IKBKAP); this mutation leads to variable skipping of exon 20 and to a drastic reduction of ELP1 in the nervous system. Clinically, many of the debilitating aspects of the disease are related to a progressive loss of proprioception; this loss leads to severe gait ataxia, spinal deformities, and respiratory insufficiency due to neuromuscular incoordination. There is currently no effective treatment for FD, and the disease is ultimately fatal. The development of a drug that targets the underlying molecular defect provides hope that the drastic peripheral neurodegeneration characteristic of FD can be halted. We demonstrate herein that the FD mouse TgFD9;Ikbkap
Identifiants
pubmed: 30905397
pii: S0002-9297(19)30054-0
doi: 10.1016/j.ajhg.2019.02.009
pmc: PMC6451698
pii:
doi:
Substances chimiques
Elp1 protein, human
0
Transcriptional Elongation Factors
0
Kinetin
P39Y9652YJ
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
638-650Subventions
Organisme : NINDS NIH HHS
ID : R37 NS095640
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007748
Pays : United States
Informations de copyright
Copyright © 2019 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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