A splice variant in <i>ATAD3A</i> expands the clinical and genetic spectrum of Harel-Yoon syndrome

Abstract

ATAD3A is a mitochondrial AAA + ATPase protein localized between the inner and outer mitochondrial membrane1; its role includes the stabilization of mitochondrial DNA, the regulation of mitochondrial fission/fusion, and the regulation of cholesterol homeostasis.1,2 Harel-Yoon syndrome (HYS) can result from biallelic deletions in the ATAD3 gene cluster (containing ATAD3A , ATAD3B , and ATAD3C ) and is associated with cerebellar and brainstem atrophy, hypotonia, encephalopathy, and death in the first days and weeks of life.3,4 A less severe presentation has been reported in those with biallelic missense variants.4,5 This attenuated form of HYS presents with developmental delay, cataracts, seizures, and optic and cerebellar atrophy with individuals living into adulthood.4,5 The findings are consistent with a genotype-phenotype correlation based on the variant type.6,7 The authors thank and acknowledge the patient and her family for their participation in this study. Also, the authors would like to acknowledge the Care4Rare Research Consortium.