Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient.

The carnitine-acylcarnitine carrier (CAC) catalyzes the translocation of long-chain fatty acids across the inner mitochondrial membrane. We cloned and sequenced the human CAC cDNA, which has an open reading frame of 903 nucleotides. Northern blot studies revealed different expression levels of CAC in various human tissues. Furthermore, mutation analysis was performed for a CAC-deficient infant. Direct sequencing of the patient's cDNA revealed a homozygous cytosine nucleotide insertion. This insertion provokes a frameshift and an extension of the open reading frame with 23 novel codons. This is the first report documenting a mutation, in the CAC cDNA, responsible for mitochondrial beta-oxidation impairment.