The mechanism of mutations in heterochromatin-related genes in autism

Mutations in different types of chromatin regulators are associated with autism. In many cases, the mutation disrupts the expression of one copy of the gene or causes a reduction in the expression of the protein.

Sagiv Shifman and his colleagues at The Hebrew University of Jerusalem found that gene expression changes in blood cells can be used to classify individuals into subtypes that generally match the type of mutations they carry. Mutations in genes involved in heterochromatin formation and remodeling were found to cause similar changes in gene expression in individuals with autism relative to their unaffected parents. Specifically, the protein expression levels of two different autism‐associated genes, activity-dependent neuroprotective protein (ADNP) and Pogo transposable element with ZNF domain (POGZ), are lower in individuals with autism.

They also found that cells from individuals with ADNP or POGZ mutations have changes in expression that point to abnormal cell division. Cells with mutations in those genes are less likely to be in the middle of cell division; the researchers speculate that this is probably because the mutant proteins play roles in cell division progression.