Prenatal onset of mitochondrial disease is associated with sideroflexin 4 deficiency

We present a third case with complex I deficiency associated with novel mutations in SFXN4. Our patient presented with intrauterine growth retardation, neonatal lactic acidosis, and developed macrocytic anemia and optic nerve hypoplasia. Muscle mitochondrial investigations revealed ultrastructural abnormalities, severe deficiency of complex I enzyme activity, and loss of subunit proteins. Whole-exome sequencing revealed bi-allelic SFXN4 mutations: a 1-base deletion, c.969delG, leading to frameshift and a premature stop codon, p.(Gln323Hisfs*20), and a stop-loss mutation in the C-terminal region, c.1012 T > C; p.(*388Glnext2), resulting in elongation of the protein by two amino acids. Expression analysis of mRNA from muscle showed loss of SFXN4 transcripts.
Source: Mitochondrion - Category: Biochemistry Source Type: research