NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms

Mitochondrial complex I (CI) deficiency is the most common oxidative phosphorylation disorder described. It shows a wide range of phenotypes with poor correlation within genotypes. Herein we expand the clinics and genetics of CI deficiency in the brazilian population by reporting three patients with pathogenic (c.640G>A, c.1268C>T, c.1207dupG) and likely pathogenic (c.766C>T) variants in the NDUFV1 gene. We show the mutation c.766C>T associated with a childhood onset phenotype of hypotonia, muscle weakness, psychomotor regression, lethargy, dysphagia, and strabismus. Additionally, this mutation was found to be associated with headaches and exercise intolerance in adulthood. We also review reported pathogenic variants in NDUFV1 highlighting the wide phenotypic heterogeneity in CI deficiency.

Automated summary

Mitochondrial complex I (CI) deficiency is the most common oxidative phosphorylation disorder, with a wide range of phenotypes and poor correlation within genotypes. This study in the Brazilian population expands the understanding of CI deficiency by reporting patients with pathogenic and likely pathogenic variants in the NDUFV1 gene, highlighting the phenotypic heterogeneity in CI deficiency. The mutation c.766C>T is associated with childhood onset symptoms and later complications in adulthood, such as headaches and exercise intolerance.