Brain Gene Co-Expression Network Analysis Identifies 22q13 Region Genes Associated with Autism, Intellectual Disability, Seizures, Language Impairment, and Hypotonia

Genes (Basel). 2023 Oct 26;14(11):1998. doi: 10.3390/genes14111998.

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.

Keywords: 22q13 deletion; Phelan–McDermid syndrome; WGCNA; candidate gene selection; neurological phenotypes.

MeSH terms

  • Autism Spectrum Disorder* / genetics
  • Autistic Disorder*
  • Brain
  • Humans
  • Intellectual Disability* / genetics
  • Language Development Disorders* / genetics
  • Muscle Hypotonia / genetics
  • Nerve Tissue Proteins / genetics
  • Seizures
  • Transcription Factors

Substances

  • Nerve Tissue Proteins
  • TCF20 protein, human
  • Transcription Factors

Supplementary concepts

  • Telomeric 22q13 Monosomy Syndrome