Brain Gene Co-Expression Network Analysis Identifies 22q13 Region Genes Associated with Autism, Intellectual Disability, Seizures, Language Impairment, and Hypotonia
Author:
Shah Snehal12ORCID, Sarasua Sara M.1ORCID, Boccuto Luigi1ORCID, Dean Brian C.3, Wang Liangjiang24
Affiliation:
1. Healthcare Genetics and Genomics, School of Nursing, Clemson University, Clemson, SC 29634, USA 2. Department of Genetics and Biochemistry, Clemson University, Clemson, SC 29634, USA 3. School of Computing, Clemson University, Clemson, SC 29634, USA 4. Center for Human Genetics, Clemson University, Greenwood, SC 29646, USA
Abstract
Phelan–McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder caused by 22q13 region deletions or SHANK3 gene variants. Deletions vary in size and can affect other genes in addition to SHANK3. PMS is characterized by autism spectrum disorder (ASD), intellectual disability (ID), developmental delays, seizures, speech delay, hypotonia, and minor dysmorphic features. It is challenging to determine individual gene contributions due to variability in deletion sizes and clinical features. We implemented a genomic data mining approach for identifying and prioritizing the candidate genes in the 22q13 region for five phenotypes: ASD, ID, seizures, language impairment, and hypotonia. Weighted gene co-expression networks were constructed using the BrainSpan transcriptome dataset of a human brain. Bioinformatic analyses of the co-expression modules allowed us to select specific candidate genes, including EP300, TCF20, RBX1, XPNPEP3, PMM1, SCO2, BRD1, and SHANK3, for the common neurological phenotypes of PMS. The findings help understand the disease mechanisms and may provide novel therapeutic targets for the precise treatment of PMS.
Funder
National Institute of General Medical Sciences of the National Institutes of Health
Subject
Genetics (clinical),Genetics
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