Branched chain acyltransferase absence due to an Alu-based genomic deletion allele and an exon skipping allele in a compound heterozygote proband expressing maple syrup urine disease

Maple syrup urine disease in the Austronesian aboriginal tribe Paiwan of Taiwan: a novel DBT (E2) gene 4.7 kb founder deletion caused by a nonhomologous recombination between LINE-1 and Alu and the carrier-frequency determination

“…6,7,12 -14 However, large deletion of the E2 gene has only been reported once as a 15 -20 kb genomic DNA loss resulting from the recombination between an intronic Alu in intron 6 and the coding sequences of the terminal exon 11. 15 Here we report another large fragment deletion in the E2 gene. This E2 4.7 kb genomic DNA deletion may lead to failure to splice intron 10 or to alternative splicing of intron 10 with several possible cryptic splice acceptor sites in the nondeleted intron 10 or nondeleted 3 0 UTR according to the analysis with BDGP: Splice Site Prediction by Neural Network (http://www.fruitfly.org/seq_tools/splice.html) (data not shown).…”

Human mutations affecting branched chain a-ketoacid dehydrogenase

“…Since all cells with mitochondria express BCKD, any cell of this type can be used; most often transformed lymphocytes. Analysis of DNA from the parents confirms inheritance and identifies the parental origin of each mutant allele (75,78). Only one mutation is found with an increased frequency, the 1325T→A transversion that results in a Y393N substitution in E1α.…”

“…Western blots determine the antigenic presence of the proteins and an absence of E2 indicates mutations in that gene (75). Mutations in either E1α orE1β can decrease the presence of both since these two proteins must assume their tetrameric structure to stabilize each against degradation (76,77).…”

Molecular basis of intermittent maple syrup urine disease: novel mutations in the E2 gene of the branched-chain α-keto acid dehydrogenase complex

“…Molecular defects in the BCKDH have been characterized in the classical, intermediate, and thiamine-responsive phenotypes (Chuang and Shih 1995;Indo and Matsuda 1996;Danner and McKean 1996). The classical phenotype is caused by mutation of any of the E1α (Zhang et al 1989;Matsuda et al 1990;Fisher et al 1991a), E1 , or E2 genes Herring et al 1992). The intermediate and thiamine-responsive phenotypes are due to mutations of E1α and E2 (Fisher et al 1991b), respectively.…”