Mutations in the Mitochondrial Complex I Assembly Factor NDUFAF1 Cause Fatal Infantile Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) describes abnormal thickening and dysfunction of heart muscle. It is a severe disorder and affected children frequently die of heart failure in infancy. Mitochondria are ‘batteries’ responsible for energy production inside most human cells. Mitochondrial disease can cause infantile-onset HCM by impairing energy production inside heart muscle cells. It is very difficult to identify the responsible gene in mitochondrial HCM, because so many genes can cause mitochondrial disease. However, identification of the precise genetic basis has important implications for prognosis, genetic counselling and prenatal diagnosis. We now show that two new mutations in a gene called NDUFAF1 caused HCM in a baby girl who died at 7 months. The NDUFAF1 gene encodes a protein needed to assemble the 45 protein components of mitochondrial complex I in a coordinated way in the inner mitochondrial membrane. This is only the second patient reported with NDUFAF1 mutations and the first to present with fatal infantile HCM. (By Elisa Fassone, http://jmg.bmj.com/content/48/10/691 )