Description:
TRIFUNCTIONAL PROTEIN DEFICIENCY
HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, BETA SUBUNIT; HADHB
Repository
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NIGMS Human Genetic Cell Repository
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Subcollection |
Heritable Diseases |
Class |
Disorders of Lipid Metabolism |
Cell Type
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Fibroblast
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Tissue Type
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Skin
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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
|
proband
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Confirmation
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Clinical summary/Case history
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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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|
Passage Frozen |
14 |
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IDENTIFICATION OF SPECIES OF ORIGIN |
Species of Origin confirmed by LINE assay |
|
Gene |
HADHB |
Chromosomal Location |
2p23 |
Allelic Variant 1 |
143450.0002; TRIFUNCTIONAL PROTEIN DEFICIENCY, TYPE 2 |
Identified Mutation |
ARG61HIS; In a male Caucasian patient who presented with hypoglycemia, hyperammonemia, mild liver dysfunction, and 3-hydroxydicarboxylic aciduria at 4 months of age, Ushikubo et al. (1996) described compound heterozygosity for an arg61-to-his mutation and an arg247-to-his (143450.0003) mutation in the HADHB gene. These were due to nucleotide substitutions 182G-A and 740G-A, respectively.
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|
Gene |
HADHB |
Chromosomal Location |
2p23 |
Allelic Variant 2 |
143450.0003; TRIFUNCTIONAL PROTEIN DEFICIENCY, TYPE 2 |
Identified Mutation |
ARG247HIS; See (143450.0002) and Ushikubo et al. (1996).
|
Remarks |
Clinically affected; presented at 3 months of age with hypoglycemia, hyperammonemia, mild liver dysfunction and 3-hydroxydicarboxylic aciduria; diagnosed at age 13 with recurrent hypoglycemia, progressive myopathy, and peripheral neuropathy; plasma acylcarnitine profile characteristic of LCHAD deficiency and enzyme testing showed complete trifunctional protein deficiency [patient #3 in Am J Hum Genet 58:979-988 (1996) - sex in this publication was incorrectly listed as male]; donor subject is a compound heterozygote; one allele has a G>A transition at nucleotide 182 of the HADHB gene [182G>A] resulting in a substitution of histidine for arginine at codon 61 [Arg61His (R61H)] and a second allele has a G>A transition at nucleotide 740 of the HADHB gene [740G>A] resulting in a substitution of histidine for arginine at codon 247 [Arg247His (R247H)]. |
Raimo S, Zura-Miller G, Fezelinia H, Spruce LA, Zakopoulos I, Mohsen AW, Vockley J, Ischiropoulos H, Mitochondrial morphology, bioenergetics and proteomic responses in fatty acid oxidation disorders Redox biology41:101923 2021 |
PubMed ID: 33725513 |
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Ushikubo S, Aoyama T, Kamijo T, Wanders RJ, Rinaldo P, Vockley J, Hashimoto T, Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits. Am J Hum Genet58(5):979-88 1996 |
PubMed ID: 8651282 |
Passage Frozen |
14 |
Split Ratio |
1:4 |
Temperature |
37 C |
Percent CO2 |
5% |
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 |
Substrate |
None specified |
Subcultivation Method |
trypsin-EDTA |
Supplement |
- |
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