Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability.

Details

Serval ID
serval:BIB_EBFCA5108DAA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability.
Journal
Genome medicine
Author(s)
Reggiani C., Coppens S., Sekhara T., Dimov I., Pichon B., Lufin N., Addor M.C., Belligni E.F., Digilio M.C., Faletra F., Ferrero G.B., Gerard M., Isidor B., Joss S., Niel-Bütschi F., Perrone M.D., Petit F., Renieri A., Romana S., Topa A., Vermeesch J.R., Lenaerts T., Casimir G., Abramowicz M., Bontempi G., Vilain C., Deconinck N., Smits G.
ISSN
1756-994X (Electronic)
ISSN-L
1756-994X
Publication state
Published
Issued date
19/07/2017
Peer-reviewed
Oui
Volume
9
Number
1
Pages
67
Language
english
Notes
Publication types: Case Reports ; Journal Article
Publication Status: epublish
Abstract
Tissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders.
Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play.
Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients' clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories.
While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases.

Keywords
Animals, Child, Developmental Disabilities/genetics, Developmental Disabilities/metabolism, Exons, Female, Guanylate Kinases/genetics, Humans, Intellectual Disability/genetics, Intellectual Disability/metabolism, Male, Membrane Proteins/genetics, Mice, Promoter Regions, Genetic, Tumor Suppressor Proteins/genetics, DLG2, Functional genomics, Intellectual disability, Neurodevelopmental disorders, Promoters
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2017 17:50
Last modification date
20/08/2019 17:14
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