A deletion mutation in the ApoC-II gene (ApoC-II Nijmegen) of a patient with a deficiency of apolipoprotein C-II.

The apolipoprotein C-II gene from a patient with a deficiency of apoC-II was cloned and sequenced. A single base deletion of a guanosine at position 2943 in exon three of the gene of the proband was identified by sequence analysis. This point mutation results in a shift of the reading frame and introduces a premature termination codon (TGA) at a position in the gene immediately following amino acid 17 of the mature C-II apolipoprotein. This single base deletion results in the loss of a normally occurring HphI restriction enzyme site in the apoC-II gene. Amplification of the mutant DNA sequence by the polymerase chain reaction and restriction enzyme digestion with HphI established that the patient is a homozygote for the base deletion. No apoC-II was detectable in the patient's plasma by two-dimensional gel electrophoresis and immunoblotting. We propose that the guanosine deletion is the primary genetic defect in this kindred leading to premature termination and formation of a nonfunctional truncated 17-amino acid C-II apolipoprotein which ultimately results in apoC-II deficiency.