Disruption of chromatin organisation causes MEF2C gene overexpression in intellectual disability: a case report.
Intellectual disability (ID)
MEF2C
Topologically associated domains (TAD)
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
02 08 2019
02 08 2019
Historique:
received:
23
01
2019
accepted:
15
07
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
31
1
2020
Statut:
epublish
Résumé
Balanced structural variants are mostly described in disease with gene disruption or subtle rearrangement at breakpoints. Here we report a patient with mild intellectual deficiency who carries a de novo balanced translocation t(3;5). Breakpoints were fully explored by microarray, Array Painting and Sanger sequencing. No gene disruption was found but the chromosome 5 breakpoint was localized 228-kb upstream of the MEF2C gene. The predicted Topologically Associated Domains analysis shows that it contains only the MEF2C gene and a long non-coding RNA LINC01226. RNA studies looking for MEF2C gene expression revealed an overexpression of MEF2C in the lymphoblastoid cell line of the patient. Pathogenicity of MEF2C overexpression is still unclear as only four patients with mild intellectual deficiency carrying 5q14.3 microduplications containing MEF2C are described in the literature. The microduplications in these individuals also contain other genes expressed in the brain. The patient presented the same phenotype as 5q14.3 microduplication patients. We report the first case of a balanced translocation leading to an overexpression of MEF2C similar to a functional duplication.
Sections du résumé
BACKGROUND
Balanced structural variants are mostly described in disease with gene disruption or subtle rearrangement at breakpoints.
CASE PRESENTATION
Here we report a patient with mild intellectual deficiency who carries a de novo balanced translocation t(3;5). Breakpoints were fully explored by microarray, Array Painting and Sanger sequencing. No gene disruption was found but the chromosome 5 breakpoint was localized 228-kb upstream of the MEF2C gene. The predicted Topologically Associated Domains analysis shows that it contains only the MEF2C gene and a long non-coding RNA LINC01226. RNA studies looking for MEF2C gene expression revealed an overexpression of MEF2C in the lymphoblastoid cell line of the patient.
CONCLUSIONS
Pathogenicity of MEF2C overexpression is still unclear as only four patients with mild intellectual deficiency carrying 5q14.3 microduplications containing MEF2C are described in the literature. The microduplications in these individuals also contain other genes expressed in the brain. The patient presented the same phenotype as 5q14.3 microduplication patients. We report the first case of a balanced translocation leading to an overexpression of MEF2C similar to a functional duplication.
Identifiants
pubmed: 31375103
doi: 10.1186/s12920-019-0558-8
pii: 10.1186/s12920-019-0558-8
pmc: PMC6679470
doi:
Substances chimiques
Chromatin
0
MEF2 Transcription Factors
0
MEF2C protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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