Characterization of compound missense mutation and deletion of carnitine palmitoyltransferase II in a patient with adenovirus-associated encephalopathy

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 halflives
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.G249
EfsX16)] abolished enzyme activity and showed short half-life. Conclusion : 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.

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