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

Abstract

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