A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.

Abstract

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.

• Authors: S S Fojo, P Lohse, C Parrott, G Baggio, C Gabelli, F Thomas, J Hoffman, H B Brewer Jr
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 84 Issue 4 Pg. 1215-9 (Oct 1989) ISSN: 0021-9738 [Print] United States
• PMID: 2477392 (Publication Type: Journal Article)

Chemical References

• Apolipoprotein C-II
• Apolipoproteins C
• Codon
• RNA
• Cytosine
• DNA
• Adenosine

Topics

• Adenosine (genetics)
• Apolipoprotein C-II
• Apolipoproteins C (genetics)
• Blotting, Northern
• Blotting, Southern
• Codon
• Cytosine
• DNA (analysis, genetics)
• Electrophoresis, Agar Gel
• Electrophoresis, Gel, Two-Dimensional
• Humans
• Mutation
• Nucleic Acid Hybridization
• Pedigree
• Polymerase Chain Reaction
• RNA (analysis)