PDHA1 and Intellectual disability: Five (15%) families had de novo diagnostic variants in nuclear-mitochondrial genes (AIFM1, LONP1, and PDHA1 and two with de novo duplications in the ATAD3 gene cluster) compared with 29% (19/65) of families with non-mitochondrial disorders having a de novo diagnosis (fig 6), particularly those with intellectual disability or epileptic encephalopathy.