PMC:4157140 / 2773-4412
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4157140","sourcedb":"PMC","sourceid":"4157140","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4157140","text":"COX deficiency (MIM 220110) is one of the most common biochemical abnormalities found in mitochondrial disorders, but about half of all cases remain genetically undefined.4 Mutations in mtDNA or nuclear DNA genes encoding COX subunits are exceptionally rare, suggesting that direct damage of the structural components of cIV is likely to cause embryonic lethality in most cases. Conversely, early-onset COX deficiency is often due to mutations in assembly factors of the enzyme,5 SURF1 (MIM 185620) being the most commonly affected gene.6,7 SURF1 mutant individuals typically present with Leigh syndrome (LS), an early-onset, rapidly progressive encephalopathy characterized by bilateral focal necrotizing lesions in the basal ganglia and brainstem nuclei. In addition, a number of mutations in genes involved in mtDNA expression or translation are consistently associated with isolated or predominant COX deficiency,8–11 including some mutations in mitochondrial tRNA-encoding genes or in nuclear-encoded mtDNA translation proteins (e.g., LRPPRC [MIM 607544] or several mitochondrial aminoacyl tRNA synthetases). As part of a long-standing project aimed at identifying novel genes responsible for COX deficiency, we present here the identification of deleterious mutations in APOPT1 (Apoptogenic-1, previously APOP-1 or C14ORF153), encoding a mitochondrial protein. This gene was identified by whole-exome sequencing (WES) analysis in three individuals from independent cohorts of subjects with isolated COX deficiency and subsequently in three additional unrelated children on the basis of a distinctive brain MRI pattern present in all.","tracks":[{"project":"2_test","denotations":[{"id":"25175347-22729865-2048442","span":{"begin":171,"end":172},"obj":"22729865"},{"id":"25175347-22729855-2048443","span":{"begin":478,"end":479},"obj":"22729855"},{"id":"25175347-9837813-2048444","span":{"begin":539,"end":540},"obj":"9837813"},{"id":"25175347-23829769-2048444","span":{"begin":539,"end":540},"obj":"23829769"},{"id":"25175347-20225024-2048445","span":{"begin":919,"end":921},"obj":"20225024"},{"id":"25175347-12529507-2048445","span":{"begin":919,"end":921},"obj":"12529507"},{"id":"25175347-24161539-2048445","span":{"begin":919,"end":921},"obj":"24161539"},{"id":"25175347-24808023-2048445","span":{"begin":919,"end":921},"obj":"24808023"}],"attributes":[{"subj":"25175347-22729865-2048442","pred":"source","obj":"2_test"},{"subj":"25175347-22729855-2048443","pred":"source","obj":"2_test"},{"subj":"25175347-9837813-2048444","pred":"source","obj":"2_test"},{"subj":"25175347-23829769-2048444","pred":"source","obj":"2_test"},{"subj":"25175347-20225024-2048445","pred":"source","obj":"2_test"},{"subj":"25175347-12529507-2048445","pred":"source","obj":"2_test"},{"subj":"25175347-24161539-2048445","pred":"source","obj":"2_test"},{"subj":"25175347-24808023-2048445","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#bf93ec","default":true}]}]}}