How do alterations in epigenetic mechanisms cause intellectual disability?

Abstract

Intellectual disability is associated with many syndromes, its main symptom includes low IQ. There are a variety of genetic and non-genetic causes of ID including environmental factors, chromosomal aberrations and single gene mutations. One example of ID that have been explored have to do with the enzyme ATRX which enhances transcription and remodels chromatin. Due to its involvement in chromatin remodeling ATRX can affect the expression of genes, through turning genes on. ATRX assists learning and memory hence leading to ID when organisms are ATRX-null. Chromatin remodeling enzymes can also cause ID by affecting neural progenitor generation, neural circuits and neural migration. These syndromes assist in comprehending the logistics in the KAT5 syndrome. The KAT5 syndrome comprises variants in the KAT5 enzyme and causes detrimental effects on neurodevelopment, leading to ID. TIP60-CB and acetyl-coA binding domains are 2 key domains in the lysine acetyltransferase enzyme (KAT5), mutations in these domains have been studied and have proven to cause ID. This data suggests that reduced acetyl of chromatin in neural cells, may lead to an impairment in cognition and memory (ID).

Keywords: Intellectual disability, neurodevelopment, chromosome, DNA, ATRX, Epigenetic, Chromatin remodeling, KAT5, histone, TIP60-CB, Acetyl-coA and DNA acetylation.

DOI: 10.7176/JMPB/72-08

Publication date: November 30^th 2022