English: A Pedigree diagram showing segregation of the SDHD c.205 G > A; p.(Glu69Lys) variant. Genotypes are shown beneath generations IV and V (+, c.205 G > A; −, WT). Affected individuals were homozygous for SDHD c.205 G > A, DNA was available from all but one affected individual (V:5). B Electropherogram showing the DNA sequence at the position of SDHD c.205 G > A in a homozygous affected individual. C T1- and T2-weighted axial views of MRI head of individual V:2 (aged 8 months). Normal myelination and no intracranial abnormalities. D Image of affected individual V:4, illustrating the absence of any facial dysmorphism. E (i) Schematic localisation of SDHD p.(Glu69Lys), p.(Asp92Gly) and p.(Ter160LeuextTer3) variants within the succinate dehydrogenase cytochrome b small subunit (CybS) domain of the SDHD polypeptide. The orange rectangle denotes the transit peptide (TP) domain, the red circle denotes the iron (haem axial ligand) binding site shared with SDHC and the blue circle denotes the ubiquinone binding site shared with SDHB. (ii) Conservation of the SDHD p.(Glu69Lys), p.(Asp92Gly) and p.(Ter160LeuextTer3) variants across species. F Visual depiction of the two autozygous regions on chromosome 11 (shown in red) common to affected individuals V:2, V:4 and V:6 including the 2.37 Mb region containing 21 genes including SDHD.