A newly discovered ASD associated mutation affects proteasome-linked protein homeostasis

What is it about?

Using whole-exome sequencing in a Lebanese family with an autistic patient, we uncovered a novel risk variant pertaining to the UBLCP1 gene. We subsequently conducted functional studies on fibroblasts of the patient & control individuals to assess the cellular and molecular effects of this mutation and how they may be linked to the development of autism. Finally, Gentamicin was used to correct for the effects of the mutation and its resultant cellular and molecular phenotype.

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Photo by Sangharsh Lohakare on Unsplash

Photo by Sangharsh Lohakare on Unsplash

Why is it important?

This work is very important for several reasons. First and foremost, it offers insight into a novel autism-associated mutation in a gene previously undescribed as ASD associated in the literature. Moreover, it provides a comprehensive look into the nature of the mutation, its effect on the UBLCP1 protein structure, as well as the consequences on several associated cellular processes such as proteasome activity and protein degradation. It also sheds light on the aminoglycoside Gentamicin as having the potential to reverse the observed phenotype in the autistic cells, hinting at the fact that although gentamicin cannot be used as autism treatment long term in humans due to its side effects, stop-codon readthrough therapy via other drugs might prove quite effective in such similar situations.