Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder
Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental...
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doaj-e907dcfe90b342f2848ded27fac9d4cc2020-11-24T22:00:26ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-04-011647627764310.3390/ijms16047627ijms16047627Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum DisorderSureni V. Mullegama0Joseph T. Alaimo1Li Chen2Sarah H. Elsea3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USARoughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.http://www.mdpi.com/1422-0067/16/4/7627MBD5ASDnetworksoverlapping phenotypesUBE3ATCF4MEF2CEHMT1RAI1transcriptional regulationpathwaysnetwork analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sureni V. Mullegama Joseph T. Alaimo Li Chen Sarah H. Elsea |
spellingShingle |
Sureni V. Mullegama Joseph T. Alaimo Li Chen Sarah H. Elsea Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder International Journal of Molecular Sciences MBD5 ASD networks overlapping phenotypes UBE3A TCF4 MEF2C EHMT1 RAI1 transcriptional regulation pathways network analysis |
author_facet |
Sureni V. Mullegama Joseph T. Alaimo Li Chen Sarah H. Elsea |
author_sort |
Sureni V. Mullegama |
title |
Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder |
title_short |
Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder |
title_full |
Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder |
title_fullStr |
Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder |
title_full_unstemmed |
Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder |
title_sort |
phenotypic and molecular convergence of 2q23.1 deletion syndrome with other neurodevelopmental syndromes associated with autism spectrum disorder |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-04-01 |
description |
Roughly 20% of autism spectrum disorders (ASD) are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5) is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention. |
topic |
MBD5 ASD networks overlapping phenotypes UBE3A TCF4 MEF2C EHMT1 RAI1 transcriptional regulation pathways network analysis |
url |
http://www.mdpi.com/1422-0067/16/4/7627 |
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