Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1

Abstract

We report clinical, metabolic, genetic and neuroradiological findings in five patients from three different families with isolated complex I deficiency. Genetic analysis revealed mutations in NDUFS1 in three patients and in NDUFV1 in two patients. Four of the mutations are novel and affect amino acid residues that either are invariant among species or conserved in their properties. The presented clinical courses are characterized by leukoencephalopathy or early death and expand the already heterogeneous phenotypic spectrum. A literature review was performed, showing that patients with mutations in NDUFS1 in general have a worse prognosis than patients with mutations in NDUFV1.

Keywords: Leukoencephalopathies; MITOCHONDRIAL encephalomyopathies; Mitochondrial complex I deficiency; NADH-ubiquinone oxidoreductase Fe–S protein 1 (NDUFS1) mutations; NADH-ubiquinone oxidoreductase flavoprotein 1 (NDUFV1) mutations.