Pyruvate dehydrogenase deficiency as a result of splice-site mutations in the PDX1 gene.
Mutations in the E3-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 E3-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 E3-binding protein deficiency and indicate yet again the high frequency of splicing mutations in this gene.
Dey
Runu
R
Laboratoire CERTO, Faculté de Medécine Necker, 156 rue de Vaugirard, Paris, France.
Aral
Bernard
B
Abitbol
Marc
M
Marsac
Cecile
C
D000595:Amino Acid Sequence; D001483:Base Sequence; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D007888:Leigh Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000235:genetics*; D011768:Pyruvate Dehydrogenase Complex / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D017384:Sequence Deletion
C045867:PDHX protein, human; D010455:Peptides; D011768:Pyruvate Dehydrogenase Complex; D022821:RNA Splice Sites; D019344:Lactic Acid