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Pyruvate dehydrogenase (PDH) deficiency caused by a 21-base pair insertion mutation in the Elα subunit

par De Meirleir, Linda;Lissens, Willy;Liebaers, Ingeborg ;Vamos, Eszter
Référence Human genetics, 88, 6, page (649-652)
Publication Publié, 1992-03

Article révisé par les pairs

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Résumé :

We report the molecular characterization of a case of a functional PDH-El (E1 subunit of pyruvate dehydrogenase) deficiency, a cause of severe congenital lactic acidosis. Residual PDH-El activity was reduced to 10% of normal values, although the subunit appeared to be quantitatively and qualitatively normal at the protein level as determined by Western blotting. The sequence of PDH-Elα mRNA and the corresponding genomic DNA revealed an in-frame 21-bp insertion between codons 305 and 306 of the normal Ela cDNA. The mutational insert commences with a novel GAT codon and is a nearly perfect tandem duplication of the wild type DNA sequence. A serine phosphorylation site regulating the activity of the PDH complex is altered by this insertion, which in all likelihood is responsible for the functional enzymatic deficiency leading to lactic acidosis. © 1992 Springer-Verlag.