Fig. 3.

Molecular and biochemical findings in the patient. (a) Results of the autozygosity mapping of the patient, a child of consanguineous parents. The red bars depict the autozygous genomic blocks of a total of 55.6 Mbp, which likely contain the disease mutation. Potentially pathogenic homozygous variants in the autozygous blocks are discussed in Supplementary Table 1. Mitochondria associated genes within the autozygous blocks (n = 17 from a total of 1,130 “mitochondrial” genes) are also listed on Supplementary Table 1. (b) Sequence electropherograms of the patient and of a wildtype control depicting the localization of the homozygous mutation. (c) High evolutionary conservation of the mutated amino acid down to Caenorhabditis elegans. (d) Biochemical flow scheme of the tricarboxylic acid cycle (TCA) and enzymes that act downstream of 2-ketoglutarate (2-KG), which is an intermediate of the TCA. GHB γ-hydroxybutyrate, SSA succinic semialdehyde, HOT hydroxyacid-oxoacid transhydrogenase, NAD nicotinamide adenine dinucleotide, L-malDH L-malate dehydrogenase, FAD flavin adenine dinucleotide, D-2-HGDH D-2-hydroxyglutarate dehydrogenase, L-2-HGDH L-2-hydroxyglutarate dehydrogenase