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Research Article Free access | 10.1172/JCI113756

Donor splice site mutation in the apolipoprotein (Apo) C-II gene (Apo C-IIHamburg) of a patient with Apo C-II deficiency.

S S Fojo, U Beisiegel, U Beil, K Higuchi, M Bojanovski, R E Gregg, H Greten, and H B Brewer Jr

Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Molecular Disease Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.

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Published November 1, 1988 - More info

Published in Volume 82, Issue 5 on November 1, 1988
J Clin Invest. 1988;82(5):1489–1494. https://doi.org/10.1172/JCI113756.
© 1988 The American Society for Clinical Investigation
Published November 1, 1988 - Version history
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Abstract

The DNA, RNA, and protein of apo C-II have been analyzed in a patient with apo C-II deficiency (apo C-IIHamburg). Markedly reduced levels of plasma and intrahepatic C-II apolipoprotein were demonstrated by immunoblotting and immunohistochemical analysis. Northern, slot blot, and in situ hybridization studies revealed low levels of a normal-sized apo C-II mRNA. No major rearrangement of the apo C-II gene was detected by Southern blotting. Sequence analysis of apo C-II genomic clones revealed a G-to-C substitution within the donor splice site of intron II. This base substitution resulted in the formation of a new Dde I and loss of a Hph I restriction enzyme cleavage site. Amplification of the mutant sequence by the polymerase chain reaction and digestion with Dde I and Hph I restriction enzymes established that the patient was homozygous for the G-to-C mutation. This is the initial report of the DNA sequence of an abnormal apo C-II gene from a patient with deficiency of apo C-II. We propose that this donor splice site mutation is the primary genetic defect that leads to defective splicing and ultimately to an apo C-II deficiency in this kindred.

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