Prenatal onset of mitochondrial disease is associated with sideroflexin 4 deficiency

• Prenatal onset of mitochondrial disease has been described in two cases with recessive mutations in the sideroflexin 4 gene (SFXN4). 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.(G1n323Hisfs*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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Complex I deficiency

Mitochondrial disease

SFXN4

Prenatal

Intrauterine growth retardation

manifestations

mutation

anemia

Cell Biology

Genetics & Heredity

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