Description:
MAPLE SYRUP URINE DISEASE (MSUD), TYPE II
DIHYDROLIPOAMIDE BRANCHED-CHAIN TRANSACYLASE; DBT
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Repository
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NIGMS Human Genetic Cell Repository
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| Subcollection |
Heritable Diseases |
| Class |
Disorders of Amino Acid Metabolism |
| Quantity |
25 µg |
| Quantitation Method |
Please see our FAQ |
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Biopsy Source
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Peripheral vein
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Cell Type
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B-Lymphocyte
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Tissue Type
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Blood
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Transformant
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Epstein-Barr Virus
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Sample Source
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DNA from LCL
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Race
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Black/African American
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Family Member
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1
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Relation to Proband
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proband
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Confirmation
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Molecular characterization after cell line submission to CCR
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Species
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Homo sapiens
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Common Name
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Human
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Remarks
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| IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis |
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| 3-methyl-2-oxobutanoate dehydrogenase |
Indo et al (J Clin Invest 80:63-70 1987) reported that lymphoblasts from this patient had BCKDH enzyme activity which showed hyperbolic kinetics for overall activity which was reduced from normal activity. Both fibroblasts and lymphoblasts showed an absence of E2 (dihydrolipoyl transacylase) protein component of the BCKDH complex using an immunoblot analysis. The E1A and E1B (branched-chain alpha-keto acid decarboxylase) and the E3 (dihydrolipoyl dehydrogenase) proteins exhibited cross-reactive peptide. Fisher et al (J Biol Chem 264:3448-3453 1989) reported that this cell culture has a type IV molecular phenotype for MSUD. Type IVs show markedly reduced E2 mRNA and E2 subunits. The authors measured the mRNA and subunit contents of the branched-chain a-keto acid dehydrogenase complex in normal and GM01366 lymphoblasts. They observed that the content of E2 mRNA is markedly lower in GM01366 lymphoblasts than in normal cells whereas the level of E1A mRNA appears to be normal in GM01366 cells. The reduced E2 mRNA level is consistent with the absence of E2 subunit in GM01366 lymphoblasts. The E1A subunit is present in normal abundance in GM01366 lymphoblasts. Litwer et al (J Biol Chem 264:14597-14600 1989) used an RNase protection assay to show the absence of transcripts for preE2b mRNA when compared with transcripts in cells with wildtype BCKD activity. EC Number: 1.2.4.4 |
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| GENE MAPPING & DOSAGE STUDIES - Y CHROMOSOME |
PCR analysis of DNA from this cell culture gave a negative result with a primer for Yq11, DYS227. |
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| Gene |
DBT |
| Chromosomal Location |
1p31 |
| Allelic Variant 1 |
E163X; MAPLE SYRUP URINE DISEASE, TYPE II |
| Identified Mutation |
GLU163TER |
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| Gene |
DBT |
| Chromosomal Location |
1p31 |
| Allelic Variant 2 |
E163X; MAPLE SYRUP URINE DISEASE, TYPE II |
| Identified Mutation |
GLU163TER |
| Remarks |
See GM01364 Fibro; HLA type A2(A9),B8, B12; 1 affected brother expired at age 14 days; deficient BCKAD activity; classical symptoms; bilateral optic atrophy and mental retardation; on diet therapy; absent E2 subunit; donor subject is homozygous for a G>T transversion in exon 6 of the DBT (E2) gene producing a premature stop codon at glu-163 [Glu163Ter (E163X)] |
| Fisher CW, Fisher CR, Chuang JL, Lau KS, Chuang DT, Cox RP, 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. Am J Hum Genet52:414-24 1993 |
| PubMed ID: 8430702 |
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| Fisher CW, Chuang JL, Griffin TA, Lau KS, Cox RP, Chuang DT, Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex. J Biol Chem264:3448-53 1989 |
| PubMed ID: 2914958 |
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| Litwer S, Herring WJ, Danner DJ, Reversion of the maple syrup urine disease phenotype of impaired branched chain alpha-ketoacid dehydrogenase complex activity in fibroblasts from an affected child. J Biol Chem264:14597-600 1989 |
| PubMed ID: 2768232 |
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| Indo Y, Kitano A, Endo F, Akaboshi I, Matsuda I, Altered kinetic properties of the branched-chain alpha-keto acid dehydrogenase complex due to mutation of the beta-subunit of the branched-chain alpha-keto acid decarboxylase (E1) component in lymphoblastoid cells derived from patients with maple syrup urine disease. J Clin Invest80:63-70 1987 |
| PubMed ID: 3597778 |
| dbSNP |
dbSNP ID: 10398 |
| Gene Cards |
DBT |
| Gene Ontology |
GO:0005515 protein binding |
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GO:0005739 mitochondrion |
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GO:0005947 alpha-ketoglutarate dehydrogenase complex (sensu Eukarya) |
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GO:0008152 metabolism |
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GO:0008415 acyltransferase activity |
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GO:0016740 transferase activity |
| NCBI Gene |
Gene ID:1629 |
| NCBI GTR |
248600 MAPLE SYRUP URINE DISEASE; MSUD |
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248610 DIHYDROLIPOAMIDE BRANCHED-CHAIN TRANSACYLASE; DBT |
| OMIM |
248600 MAPLE SYRUP URINE DISEASE; MSUD |
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248610 DIHYDROLIPOAMIDE BRANCHED-CHAIN TRANSACYLASE; DBT |
| Omim Description |
BCKD DEFICIENCY |
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BCKD, E1-ALPHA SUBUNIT, INCLUDED; BCKDE1A, INCLUDED |
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BRANCHED-CHAIN ALPHA-KETO ACID DEHYDROGENASE DEFICIENCY |
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BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, ALPHA POLYPEPTIDE, INCLUDED;BCKDHA, INCLUDED; BCKDH, INCLUDED |
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BRANCHED-CHAIN KETOACIDURIA |
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KETO ACID DECARBOXYLASE DEFICIENCYTHIAMINE-RESPONSIVE MSUD, INCLUDED |
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MAPLE SYRUP URINE DISEASE, TYPE IA |
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MSUD |
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MSUD, TYPE IA |
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