New Mutations Identified Linked to Rare Autoimmune Disease

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder. The disease has a genetic basis where mutations in both copies of the autoimmune regulator gene (AIRE) cause disease. This regulator is normally responsible for eliminating self-reactive T cells, but when mutated, has the potential to cause autoimmune disease. While there are AIRE variants known to cause APECED, not all people with APECED have the expected genetic variants.

Now, a recent study titled Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) identifies a new mutation in non-coding regions of the AIRE gene that can explain these cases of APECED.

This study examined the DNA sequences from 104 individuals with APECED. Of these 104, 17 had no hallmark AIRE mutations typically associated with APECED. The mutation the study identified leads to the inclusion of sequences in the AIRE protein that aren’t normally included, leading to the dysfunction.

This finding can help develop new genetic screenings and treatments for APECED.

Citation:

Ochoa, S., et al. (2024). A deep intronic splice–altering AIRE variant causes APECED syndrome through antisense oligonucleotide-targetable pseudoexon inclusion. Science Translational Medicine, 16(765), https://doi.org/10.1126/scitranslmed.adk0845