Occurrence of a 2-bp (AT) deletion allele and a nonsense (G-to-T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: Multiple-exon skipping as a secondary effect of the mutations

Journal Article · Mon Feb 01 04:00:00 EST 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6572448

Fisher, C W; Fisher, C R; Chuang, J L; Lau, K S; Chuang, D T; Cox, R P ^[1]

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1. Univ. of Texas, Dallas (United States)

The authors have identified two novel mutant alleles in the transacylase (E2) gene of the human branched-chain [alpha]-keto acid dehydrogenase (BCKAD) complex in 6 of 38 patients with maple syrup urine disease (MSUD). One mutation, a 2-bp (AT) deletion in exon 2 of the E2 gene, causes a frameshift downstream of residue ([minus]26) in the mitochondrial targeting presequence. The second mutation, a G-to-T transversion in exon 6 of the E2 gene, produces a premature stop codon at Glu-163 (E163*). Transfection of constructs harboring the E163* mutation into an E2-deficient MSUD cell line produced a truncated E2 subunit. However, this mutant E2 chain is unable to assemble into a 24-mer cubic structure and is degraded in the cell. The 2-bp (AT) deletion and the E163* mutant alleles occur in either the homozygous or compound-heterozygous state in the 6 of 38 unrelated MSUD patients studied. Moreover, an array of precise single- and multiple-exon deletions were observed in many amplified E2 mutant cDNAs. The latter results appear to represent secondary effects on RNA processing that are associated with the MSUD mutations at the E2 locus. 30 refs., 8 figs.

• OSTI ID: 6572448
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:2; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ACYLATION
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CLONING
DECARBOXYLATION
DETECTION
DISEASES
DNA HYBRIDIZATION
DNA SEQUENCING
DNA-CLONING
ENZYMES
GENE MUTATIONS
HYBRIDIZATION
KETO ACIDS
MITOCHONDRIA
MUTATIONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS