The variants in PDHA1 identified in P1 and P2 are synonymous, but the fact that they both were (1) shown to be de novo, (2) predicted to change ESE motifs in exons 5 and 6, (3) not found in the normal population, and (4) ATP production was decreased, with substrates malate+pyruvate in mitochondria isolated from the patient's muscle, suggested that the variants were causing PDCD in the patients. The gene discussed is PDHA1; the disease is pre-descemet corneal dystrophy.