Reducing the Cost of the Diagnostic Odyssey in Early Onset Epileptic Encephalopathies

Figure 2

KARS has two isoforms, one retained in the cytoplasm and one transported to the mitochondria. A mitochondrial targeting sequence spans exons 2 and 3; the cytoplasmic isoform skips exon 2 and is not transported. Case 3 has two inherited mutations that disrupt the gene. An Ala29Pro missense mutation alters the end of the mitochondrial targeting sequence; we predict that it is not transported, but the cytoplasmic isoform is still functional. The other allele has an approximately 8 kb deletion spanning exons 2–4, resulting in a frameshift and early termination.