Pyruvate dehydrogenase deficiency as a result of splice-site mutations in the PDX1 gene.

[pyruvate dehydrogenase deficiency]

Mutations in the E 3 -binding protein component of pyruvate dehydrogenase complex have been demonstrated in a few cases of Leigh syndrome . We report that two mutations previously detected in the E 3 -binding protein cDNA are the consequence of splice-site mutations . Both involved a single base substitution in the conserved dinucleotides of splice junctions , one leading to skipping of an exon and the other , to activation of a cryptic site . Our findings add to the understanding of molecular basis of E 3 -binding protein deficiency and indicate yet again the high frequency of splicing mutations in this gene .