Summary
The genetic defect that leads to deficiency of apoC-II in 2 patients with apoC-II deficiency from independent kindreds has been defined.
The first patient from Hamburg, West Germany, was found to have a single base substitution (guanosine for a cytosine,) at the first base of the donor splice site of intron II of the apoC-II gene by sequence analysis. This mutation should abolish normal splicing at this site and ultimately lead to the deficiency of plasma apoC-II observed in this kindred. Analysis of total RNA isolated from the patients liver by Northern, slot blot, and in situ RNA hybridization, as well as evaluation of the intrahepatic apoC-II content by immunohistochemistry confirmed the results of our sequence analysis.
The second patient from Nijmegen, the Netherlands was found to have a deletion of a cytosine at position # 2943 of exon 3 of the apoC-II gene. This mutation results in the formation of a premature termination codon at a position corresponding to amino acid #18 of normal apoC-II. As a result, this mutation leads to the formation of a truncated apoC-II that is unlikely to activate lipoprotein lipase and thus, leads to apoC-II deficiency in this kindred.
The characterization of the genetic abnormalities in the apoC-II gene of these 2 patients will further our understanding of the molecular defects that can lead to deficiency of apoC-II. These experiments also illustrate the heterogeneity of lesions that can lead to the syndrome of apoC-II deficiency.
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© 1989 Plenum Press, New York
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Fojo, S.S. et al. (1989). The Molecular Basis of ApoC-II Deficiency. In: Sirtori, C.R., Franceschini, G., Brewer, H.B., Assmann, G. (eds) Human Apolipoprotein Mutants 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9549-6_14
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DOI: https://doi.org/10.1007/978-1-4615-9549-6_14
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