Molecular characterization of 82 patients with pyruvate dehydrogenase complex deficiency. Structural implications of novel amino acid substitutions in E1 protein

► Retrospective study on 82 patients with pyruvate dehydrogenase complex (PDHc) deficiencies. ► Combination of gDNA and cDNA analyses for mutation screening in the different genes. ► 41 novel mutations reported, among them 78% in the X-linked PDHA1 gene. ► Contiguous gene deletion syndromes, mosaicism in male patients, splice aberrations identified in PDHA1. ► Prediction of the functional effect of novel PDHA1 missense mutation by structural modelling.