Mutations in the TMEM70 are the most common cause of nuclear ATP synthase deficiency resulting in a distinctive phenotype characterized by severe neonatal hypotonia, hypertrophic cardiomyopathy (HCMP), facial dysmorphism, severe lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria (3-MGA).
Mutations in the TMEM70 gene are the most common cause of nuclear encoded ATP synthase deficiency resulting in a syndrome characterized by neonatal lactic acidosis, cardiomyopathy, and encephalomyopathy.
The study identifies TMEM70 gene defect as a pan-ethnic disorder and further redefines it as the most common cause of nuclear-origin ATP synthase deficiency.
The aim of this multi-site survey was to characterise the natural course of a novel mitochondrial disease with ATP synthase deficiency and mutation in the TMEM70 gene.
We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70.