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 |
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Cell Type
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Fibroblast
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Transformant
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Untransformed
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Race
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White
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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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| PDL at Freeze |
6.1 |
| Passage Frozen |
1 |
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| MITOCHONDRIAL DNA ANALYSIS |
Indo et al (J Clin Invest 80:63-70 1987) reported that these fibroblasts showed an absence of E2 (dihydrolipoyl transacylase) protein component of the BCKDH multienzyme complex using an immunoblot analysis. Eisenstein et al (Am J Hum Genet 37:A8 1985) had previously reported the same absence of the E2 protein in mitochondrial extracts of this culture using western blot analysis employing a rabbit anti-bovine kidney BCKDH antibody. Normal cross-reactive material was observed for BCKDH complex subunits E1A E1B (branched-chain alpha-keto acid decarboxylase) and E3 (dihydrolipoyl dehydrogenase). |
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| 3-methyl-2-oxobutanoate dehydrogenase |
According to the submitter, biochemical test results for this subject showed decreased enzyme activity. EC Number: 1.2.4.4; <2% activity. |
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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 |
248610.0009; MAPLE SYRUP URINE DISEASE, TYPE II |
| Identified Mutation |
2-BP DEL,AT; In several patients with classic MSUD2 (248600), Fisher et al. (1993) identified a 2-bp (AT) deletion in exon 2 of the DBT gene, causing a frameshift downstream of residue -26 in the mitochondrial targeting presequence. The mutation occurred in homozygous and compound heterozygous states. |
| Remarks |
Less than 2% of normal BCKAD activity; absence of cross-reactive material for BCKAD complex subunit E2, positive for E1A, E1B, and E3; donor subject is a compound heterozygote: one allele has a G>T transversion in exon 6 of the DBT (E2) gene producing a premature stop codon at glu-163 [Glu163Ter (E163X)] and the second allele has a 2 bp (AT) deletion in exon 2, causing a frameshift downstream of residue (-26) in the mitochondrial targeting presequence |
| 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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| 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 |
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| Yoshida I, Sweetman L, Nyhan WL, Metabolism of branched-chain amino acids in fibroblasts from patients with maple syrup urine disease and other abnormalities of branched- chain ketoacid dehydrogenase activity. Pediatr Res20:169-74 1986 |
| PubMed ID: 3080729 |
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| Eisenstein, Characterization of branch chain keto acid dehydrogenase (BCKAD) deficiency in maple syrup urine disease (MSUD). Am J Hum Genet37:A8 (1985):169-74 1985 |
| PubMed ID: 3080729 |
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| Chuang DT, Ku LS, Kerr DS, Cox RP, Detection of heterozygotes in maple-syrup-urine disease: measurements of branched-chain alpha-ketoacid dehydrogenase and its components in cell cultures. Am J Hum Genet34:416-24 1982 |
| PubMed ID: 7081220 |
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| Fensom AH, Benson PF, Baker JE, A rapid method for assay of branched-chain keto acid decarboxylation in cultured cells and its application to prenatal diagnosis of maple syrup urine disease. Clin Chim Acta87:169-74 1978 |
| PubMed ID: 668138 |
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| Dancis J, Hutzler J, Cox RP, Maple syrup urine disease: branched-chain keto acid decarboxylation in fibroblasts as measured with amino acids and keto acids. Am J Hum Genet29:272-9 1977 |
| PubMed ID: 868873 |
| dbSNP |
dbSNP ID: 21172 |
| 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 |
| Passage Frozen |
1 |
| Split Ratio |
1:3 |
| Temperature |
37 C |
| Percent CO2 |
5% |
| Percent O2 |
AMBIENT |
| Medium |
Eagle's Minimum Essential Medium with Earle's salts and non-essential amino acids with 2mM L-glutamine or equivalent |
| Serum |
15% fetal bovine serum Not inactivated |
| Supplement |
- |
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