title: Identification of a Novel HADHB Gene Mutation in an Iranian Patient with Mitochondrial Trifunctional Protein Deficiency.
abstract: BACKGROUND
  Mitochondrial trifunctional protein (MTP) is a hetero-octamer composed of eight parts (subunits): four α-subunits containing LCEH (long-chain 2,3-enoyl-CoA  hydratase) and LCHAD (long-chain 3-hydroxyacyl CoA dehydrogenase) activity, and four β-subunits that possess LCKT (long-chain  3-ketoacyl-CoA thiolase) activity which catalyzes three out of four steps in β-oxidation spiral of long-chain fatty acid. Its deficiency is an autosomal recessive disorder that causes a clinical spectrum of diseases.
  
  
  METHODS
  A blood spot was collected from the patient's original newborn screening card with parental informed consent. A newborn screening test and quantity plasma acylcarnitine profile analysis by MS/MS were performed. After isolation of DNA and Amplification of all exons of the HADHA and HADHB, directly Sequence analyses of all exons and the flanking introns both of genes were performed.
  
  
  RESULTS
  Here, we report a novel mutation in a patient with MTP deﬁciency diagnosed with newborn screening test and quantity plasma acylcarnitine profile analysis by MS/MS and then confirmed by enzyme analysis in cultured fibroblasts and direct sequencing of the HADHA and HADHB genes. Molecular analysis of causative genes showed a missense mutation (p.Q385P) c.1154A > C in exon 14 of HADHB gene.
  
  
  CONCLUSIONS
  Since this mutation was not found in 50 normal control cases; so it was concluded that c.1154A > C mutation was a causative mutation. Phenotype analysis of this mutation predicted pathogenesis which reduces the stability of the MTP protein complex.
authors.affiliation: Department of Genetics, Faculty of Science, Shahid Chamran University, Ahvaz, Iran.
authors.forename: Mahdiyeh
authors.initials: M
authors.lastname: Shahrokhi
authors.affiliation: Department of Genetics, Faculty of Science, Shahid Chamran University, Ahvaz, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shafiei
authors.affiliation: Department of Genetics, Faculty of Science, Shahid Chamran University, Ahvaz, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Galehdari
authors.affiliation: Narges Medical Genetic Laboratory, Ahvaz, Iran, Department of Medical Genetics, Jundishapur University of Medical Science, Ahvaz, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Shariati
mesh_terms: D009202:Cardiomyopathies / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D007231:Infant, Newborn; D007492:Iran; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D008297:Male; D017240:Mitochondrial Myopathies / Q000235:genetics*; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency* / Q000235:genetics; D063993:Mitochondrial Trifunctional Protein, beta Subunit / Q000235:genetics*; D020125:Mutation, Missense; D015997:Neonatal Screening; D009422:Nervous System Diseases / Q000235:genetics*; D012206:Rhabdomyolysis / Q000235:genetics*; D053719:Tandem Mass Spectrometry
chemical_list: C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit