Autosomal variants affecting nucleases that support mtDNA replication, including RNASEH1 [250,257,258], MGME1 [90,263], and DNA2 [264–266], can also cause mtDNA replication disorders, often with prominent and marked myopathy, including respiratory weakness, and a spectrum of neurological and non-neurological features, including gastrointestinal disease [16,232]. Here, MGME1 is linked to gastrointestinal disease.