Mitochondrial complex I deficiency is associated with a wide range of clinical presentations, including Leigh syndrome. Its genetic causes are heterogeneous, with poor genotype-phenotype correlation. It is impossible to identify the genetic defect of complex I deficiency using clinical observation and metabolic/imaging studies alone. As a result, whole-exome sequencing (WES) is increasingly used in clinical work to identify an underlying genetic defect causing the disease. The article in this issue of EMBO Molecular Medicine by Alahmad et al (2020) is timely and valuable, as it expands on the genotype of mitochondrial complex I deficiency by identifying and characterising pathogenic variants of the NDUFC2 gene in children with Leigh syndrome.
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.