Defective NDUFA9 as a novel cause of neonatally fatal complex I disease

Mitochondrial disorders are associated with abnormalities of the oxidative phosphorylation (OXPHOS) system and cause significant morbidity and mortality in the population. The genetic cause remains still unknown in a large part of patients with mitochondrial disease. Here we report the first disease-causing mutation in the complex I subunit encoding NDUFA9 gene, which was identified in a patient born from consanguineous parents with neonatally fatal Leigh syndrome and complex I deficiency. Our data show that homozygosity mapping followed by candidate gene analysis remain an efficient way to detect mutations even in small consanguineous pedigrees with OXPHOS deficiency, especially when the enzyme deficiency in fibroblasts allows appropriate candidate gene selection and functional complementation. (By Bianca J.C. van den Bosch, PhD, http://jmg.bmj.com/content/early/2011/11/22/jmedgenet-2011-100466.abstract?papetoc )