Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation.

Susanna TulliAndrea Del BondioValentina BadernaDavide MazzaFranca CodazziTyler Mark PiersonAlessandro AmbrosiDagmar NolteCyril GoizetCamilo ToroJonathan BaetsTine DeconinckPeter DeJonghePaola MandichGiorgio CasariFrancesca Maltecca

Published in: Journal of medical genetics (2019)

Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2+/- cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.

Keyphrases

induced apoptosis
cell cycle arrest
copy number
oxidative stress
minimally invasive
stem cells
machine learning
dna methylation
gene expression
big data
genome wide
deep learning