Microduplication of the ARID1A gene causes intellectual disability with recognizable syndromic features.
Genet Med
; 19(6): 701-710, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-27906199
ABSTRACT
PURPOSE:
To determine whether duplication of the ARID1A gene is responsible for a new recognizable syndrome.METHODS:
We describe four patients with a 1p36.11 microduplication involving ARID1A as identified by array-comparative genomic hybridization . We performed comparative transcriptomic analysis of patient-derived fibroblasts using RNA sequencing and evaluated the impact of ARID1A duplication on the cell cycle using fluorescence-activated cell sorting. Functional relationships between differentially expressed genes were investigated with ingenuity pathway analysis (IPA).RESULTS:
Combining the genomic data, we defined a small (122 kb), minimally critical region that overlaps the full ARID1A gene. The four patients shared a strikingly similar phenotype that included intellectual disability and microcephaly. Transcriptomic analysis revealed the deregulated expression of several genes previously linked to microcephaly and developmental disorders as well as the involvement of signaling pathways relevant to microcephaly, among which the polo-like kinase (PLK) pathway was especially notable. Cell-cycle analysis of patient-derived fibroblasts showed a significant increase in the proportion of cells in G1 phase at the expense of G2-M cells.CONCLUSION:
Our study reports a new microduplication syndrome involving the ARID1A gene. This work is the first step in clarifying the pathophysiological mechanism that links changes in the gene dosage of ARID1A with intellectual disability and microcephaly.Genet Med advance online publication 01 December 2016.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Cromossomos Humanos Par 1
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Proteínas Nucleares
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Duplicação Gênica
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Deficiência Intelectual
Tipo de estudo:
Etiology_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Genet Med
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França