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 fra me of 903 nucleotides. Northern blot studies revealed different expres sion levels of CAC in various human tissues. Furthermore, mutation ana lysis was performed for a CAC-deficient infant. Direct sequencing of t he patient's cDNA revealed a homozygous cytosine nucleotide insertion. This insertion provokes a frameshift and an extension of the open rea ding frame with 23 novel codons. This is the first report documenting a mutation, in the CAC cDNA, responsible for mitochondrial beta-oxidat ion impairment.