Transcriptome analysis of a ring chromosome 20 patient cohort

Myers, KA; Bennett, MF; Hildebrand, MS; Coleman, MJ; Zhou, G; Hollingsworth, G; Cairns, A; Riney, K; Berkovic, SF; Bahlo, M; Scheffer, IE

Author(s): Myers, KA; Bennett, MF; Hildebrand, MS; Coleman, MJ; Zhou, G; Hollingsworth, G; Cairns, A; Riney, K; Berkovic, SF; Bahlo, M; Scheffer, IE;
Details: Publication Year 2021-11-18,Volume 62,Issue #1,Page e22-e28
Journal Title: Epilepsia
Publication Type: Journal Article
Abstract: 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.
Publisher: Wiley
Keywords: Nprl3; Rna; focal cortical dysplasia; focal epilepsy; ring chromosome 20 syndrome; ring chromosomes; sequence analysis
Research Division(s): Population Health And Immunity
PubMed ID: 33207017
Publisher's Version: https://doi.org/10.1111/epi.16766
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2021-02-01 12:07:29

Last Modified: 2021-03-02 11:27:00