Pathological variants in TOP3A cause distinct disorders of mitochondrial and nuclear genome stability

ABSTRACT: Topoisomerase 3 (TOP3A) is an enzyme that removes torsional strain and interlinks between DNA molecules. TOP3A localises to both the nucleus and mitochondria, with the two isoforms playing specialised roles in DNA recombination and replication, respectively. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, which results from bi-allelic pathogenic variants in BLM, encoding a nuclear binding partner of TOP3A. In this work we describe eleven individuals from nine families with an adult-onset mitochondrial disease resulting from bi-allelic TOP3A gene variants. The majority of patients have a consistent clinical phenotype characterised by bilateral ptosis, ophthalmoplegia, myopathy and axonal sensory motor neuropathy. We present a comprehensive characterisation of

SUBMITTER: Ms. Direnis Erdinc 

PROVIDER: S-SCDT-10_15252-EMMM_202216775 | biostudies-other |

REPOSITORIES: biostudies-other