Molecular characterization of a 1p36 chromosomal duplication and in utero interference define ENO1 as a candidate gene for polymicrogyria.
Eur J Hum Genet
; 28(12): 1703-1713, 2020 12.
Article
in En
| MEDLINE
| ID: mdl-32488097
ABSTRACT
While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation phenotype frequently present in patients with 1p36 monosomy. The gene whose haploinsufficiency could cause this phenotype remains to be identified. We used high-resolution arrayCGH in patients with various forms of PMG in order to identify chromosomal variants associated to the malformation and characterized the genes included in these regions in vitro and in vivo. We identified the smallest case of 1p36 duplication reported to date in a patient presenting intellectual disability, microcephaly, epilepsy, and perisylvian polymicrogyria. The duplicated segment is intrachromosomal, duplicated in mirror and contains two genes enolase 1 (ENO1) and RERE, both disrupted by the rearrangement. Gene expression analysis performed using the patient cells revealed a reduced expression, mimicking haploinsufficiency. We performed in situ hybridization to describe the developmental expression profile of the two genes in mouse development. In addition, we used in utero electroporation of shRNAs to show that Eno1 inactivation in the rat causes a brain development defect. These experiments allowed us to define the ENO1 gene as the most likely candidate to contribute to the brain malformation phenotype of the studied patient and consequently a candidate to contribute to the malformations of the cerebral cortex observed in patients with 1p36 monosomy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphopyruvate Hydratase
/
Chromosomes, Human, Pair 1
/
Biomarkers, Tumor
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Tumor Suppressor Proteins
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DNA-Binding Proteins
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Chromosome Duplication
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Polymicrogyria
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Intellectual Disability
Type of study:
Prognostic_studies
Limits:
Adult
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Animals
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Female
/
Humans
Language:
En
Journal:
Eur J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2020
Document type:
Article
Affiliation country:
France