“…Subjects who were determined to be PDC enzyme deficient first at CIDEM but without a known genetic etiology were enrolled in the IRB-approved studies for molecular confirmation by either 1) Sanger sequencing for the common PDC genes ( DLAT, DLD, PDHA1, PDHB, PDHX, and PDP1 performed at CIDEM on a research or clinical basis at UHCMC Center for Human Genetics Laboratory (CHGL), 2) next-generation sequencing (NGS) of 23 genes associated with pyruvate metabolism (i.e., targeted gene panel; TGP) including BOLA3, DLAT, DLD, LIAS, LIPT1, LIPT2, NFU1, PDHA1, PDHB, PDHX, PDK1, PDK2, PDK3, PDK4, PDP1, PDP2, PC, PCK1, PCK2, SLC19A2, SLC19A3, SLC25A19 and TPK1 (performed at UHCMC CHGL), or 3) whole exome sequencing (WES; performed at the Genomics Core Facility of CWRU) [4,5]. …”