Molecular basis for congenital deficiency of alpha 2-plasmin inhibitor. A frameshift mutation leading to elongation of the deduced amino acid sequence

The Journal of Clinical Investigation
O MiuraN Aoki

Abstract

The present study was designed to elucidate the molecular genetic basis of a familial deficiency of alpha 2-plasmin inhibitor (alpha 2PI). Southern blot hybridization analysis with human alpha 2PI cDNA and genomic DNA probes demonstrated no gross deletion or rearrangement of the gene. By sequencing all the coding exons and exon-intron boundaries of the gene of a homozygote, we identified a single cytidine nucleotide insertion in the exon coding for the carboxyl-terminal region. This frameshift mutation leads to an alteration and elongation of the carboxyl-terminal portion of the deduced amino acid sequence. Synthetic oligonucleotide probes confirmed this frameshift mutation in all the affected family members including both heterozygous parents. In a transient expression assay, the alpha 2PI level in the culture medium of the cells transfected with the mutated alpha 2PI expression vector was very low and only 4% of that of the cells transfected with the normal vector, although the transcript levels and the cellular contents of alpha 2PIs did not differ significantly. Elongation of amino acid sequence in the mutant alpha 2PI was confirmed by an analysis of alpha 2PI in a transient expression experiment. These data indicate that t...Continue Reading

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Citations

Jan 1, 1991·Comparative Biochemistry and Physiology. B, Comparative Biochemistry·S D Patterson
Sep 27, 2005·Thrombosis Research·Nobuo Aoki
Jul 27, 2001·British Journal of Haematology·R FavierP de Moerloose
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Jan 25, 2003·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Michel M L HanssMarc Dechavanne
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Feb 15, 2000·The Journal of Biological Chemistry·D H ChungS Hirosawa
Dec 1, 1992·Liver·F CalleaV J Desmet

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