Transcriptome analysis of a ring chromosome 20 patient cohort.
NPRL3
RNA
focal cortical dysplasia
focal epilepsy
ring chromosome 20 syndrome
ring chromosomes
sequence analysis
Journal
Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
16
10
2019
revised:
03
09
2020
accepted:
02
11
2020
pubmed:
19
11
2020
medline:
20
4
2021
entrez:
18
11
2020
Statut:
ppublish
Résumé
Ring chromosomes occur when the ends of normally rod-shaped chromosomes fuse. In ring chromosome 20 (ring 20), intellectual disability and epilepsy are usually present, even if there is no deleted coding material; the mechanism by which individuals with complete ring chromosomes develop seizures and other phenotypic abnormalities is not understood. We investigated altered gene transcription as a contributing factor by performing RNA-sequencing (RNA-seq) analysis on blood from seven patients with ring 20, and 11 first-degree relatives (all parents). Geographic analysis did not identify altered expression in peritelomeric or other specific chromosome 20 regions. RNA-seq analysis revealed 97 genes potentially differentially expressed in ring 20 patients. These included one epilepsy gene, NPRL3, but this finding was not confirmed on reverse transcription Droplet Digital polymerase chain reaction analysis. Molecular studies of structural chromosomal anomalies such as ring chromosome are challenging and often difficult to interpret because many patients are mosaic, and there may be genome-wide chromosomal instability affecting gene expression. Our findings nevertheless suggest that peritelomeric altered transcription is not the likely pathogenic mechanism in ring 20. Underlying genetic mechanisms are likely complex and may involve differential expression of many genes, the majority of which may not be located on chromosome 20.
Substances chimiques
GTPase-Activating Proteins
0
NPRL3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e22-e28Subventions
Organisme : National Health and Medical Research Council
ID : 1091593
Informations de copyright
© 2020 International League Against Epilepsy.
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