Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex.

We report the isolation of a 22-kb human genomic clone (G7) that contains 8 exons encoding a partial mitochondrial presequence, the entire mature peptide and the complete 3' untranslated region of the E1 alpha mRNA of human branched-chain alpha-keto acid dehydrogenase complex. Based on this gene structure, exon 9 contains the Tyr393----Asn mutation previously identified in the E1 alpha subunit of Mennonite and other maple syrup urine disease (MSUD) patients. Moreover, the homozygous mutation appears to cause skipping of exon 6 in the mutant E1 alpha transcript. The information on the gene structure for the entire mature E1 alpha subunit will facilitate investigations into the molecular basis of MSUD involving this subunit.