title: Characterization of compound missense mutation and deletion of carnitine palmitoyltransferase II in a patient with adenovirus-associated encephalopathy.
abstract: BACKGROUND
  In mammals, carnitine palmitoyltransferase (CPT) system is a pivotal component of energy metabolism through mitochondrial fatty acid oxidation. The majority of patients with fatal or handicapped influenza-associated encephalopathy exhibit thermolabile compound homo/heterozygous mutations of CPT II.
  
  
  OBJECTIVE
  Compound CPT II mutations, [c.647A>G (p.Q216R)], [c.1102G>A (p.V368I)], [c.1939A>G (p.M647V)] and [c.745delG (p.G249EfsX16)], were found in a patient with adenovirus-associated encephalopathy and his family. The properties of these CPT II mutations were analyzed in COS-7 cells.
  
  
  METHODS
  CPT II mutations in the patient and his family were expressed in COS-7 cells and their molecular masses, enzyme activities, thermal instabilities and half-lives were analyzed.
  
  
  RESULTS
  We identified two novel CPT II mutations in the patient, [c.647A>G (p.Q216R)] and [c.745delG (p.G249EfsX16)]. The CPT II Q216R mutation showed mild reduction of activity, thermal instability and short half-life but compound mutations with Q216R+V368I+M647V showed further enhancement of these disabilities, although mutations V368I and M647V had no such effects. CPT II mutation [c.745delG (p.G249EfsX16)] abolished enzyme activity and showed short half-life.
  
  
  CONCLUSIONS
  The thermal instability and short half-life of the novel CPT II mutations, [c.647A>G (p.Q216R)] and [c.745delG (p.G249EfsX16)], could play important roles in energy crisis in the pathogenesis of virus-associated encephalopathy.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, University of Tokushima, Tokushima, Japan.
authors.forename: Dengbing
authors.initials: D
authors.lastname: Yao
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Miyoko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Junji
authors.initials: J
authors.lastname: Chida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000257:Adenoviridae Infections / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D019556:COS Cells; D002334:Carnitine O-Palmitoyltransferase / Q000737:chemistry / Q000235:genetics*; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D018792:Encephalitis, Viral / Q000201:enzymology* / Q000235:genetics; D004795:Enzyme Stability; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense
chemical_list: D000255:Adenosine Triphosphate; D002334:Carnitine O-Palmitoyltransferase