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Thromb Haemost 1996; 75(01): 096-100
DOI: 10.1055/s-0038-1650227
Original Article
Schattauer GmbH Stuttgart

A Novel Missense Mutation in Two Families with Congenital Plasminogen Deficiency: Identification of an Ala675 to Thr675 Substitution

N Mima
The First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima, Japan
,
H Azuma
The First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima, Japan
,
T Shigekiyo
The First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima, Japan
,
S Saito
The First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima, Japan
› Author Affiliations
Further Information

Publication History

Received 15 June 1995

Accepted after revision 18 September 1995

Publication Date:
27 July 2018 (online)

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Summary

We used a polymerase chain reaction (PCR) strategy and restriction fragment polymorphism analysis to evaluate all 19 exons of the plasminogen (PLG) gene in a Japanese patient with congenital PLG deficiency and her family members (family C). Sequence analysis following amplification of each exon and its flanking regions showed a single G to A transition in exon 17, resulting in the conversion of an Ala675 codon (GCT) to Thr675 codon (ACT). Since this mutation generates a new Mae III site, the Mae III digestion patterns of the PCR-amplified exon 17 fragments from each family member were analyzed. In all cases, the patterns correlated with the activities and antigen levels of plasma PLG in those members. The identical G to A transition in the same codon of exon 17 was detected by a Mae III digestion experiment in another proband and her family members with congenital PLG deficiency (family K). Furthermore, 20 normal individuals examined had no Mae III restriction site at this location. We conclude that a G to A transition in exon 17 is responsible for the congenital PLG deficiency inherited in these two Japanese families.

 

  • References

  • 1 Petersen TE, Martzen MR, Ichinose A, Davie EW. Characterization of gene for human plasminogen, a key proenzyme in the fibrinolytic system. J Biol Chem 1990; 265: 6104-6111
    PubMedSearch in Google Scholar
  • 2 Murray JC, Buetow KH, Donovan M, Hornung S, Motulsky AG, Disteche C, Dyer K, Swisshelm K, Anderson J, Giblett E, Sadler E, Eddy R, Shows TB. Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27. Am J Hum Genet 1987; 40: 338-350
    PubMedSearch in Google Scholar
  • 3 Cooper DN. The molecular genetics of familial venous thrombosis. Blood Rev 1991; 5: 55-70
    CrossrefPubMedSearch in Google Scholar
  • 4 Sottrup-Jensen L, Claeys H, Zajdel M, Petersen TE, Magnusson S. The primary structure of human plasminogen: isolation of two lysine-binding fragments and one “mini”-plasminogen (MW, 38,000) by elastase-cata-lyzed specific limited proteolysis. Prog Chem Fibriol Thrombol 1978; 3: 191-209
    PubMedSearch in Google Scholar
  • 5 Forsgren M, Råden B, Israelsson M, Larsson K, Hedén L-O. Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett 1987; 213: 254-260
    CrossrefPubMedSearch in Google Scholar
  • 6 Robbins KC. Dysplasminogenemias. Prog Cardiovasc Dis 1992; 34: 295-308
    CrossrefPubMedSearch in Google Scholar
  • 7 Wiman B. Primary structure of the B-chain of human plasmin. Eur J Bio-chem 1977; 76: 129-137
    CrossrefPubMedSearch in Google Scholar
  • 8 Miyata T, Iwanaga S, Sakata Y, Aoki N. Plasminogen Tochigi: Inactive plasmin resulting from replacement of alanine-600 by threonine in the active site. Proc Natl Acad Sci USA 1982; 79: 6132-6136
    CrossrefPubMedSearch in Google Scholar
  • 9 Ichinose A, Espling ES, Takamatsu J, Saito H, Shinmyozu K, Maruyama I, Petersen TE, Davie EW. Two types of abnormal genes for plasminogen in families with a predisposition for thrombosis. Proc Natl Acad Sci USA 1991; 88: 115-119
    CrossrefPubMedSearch in Google Scholar
  • 10 Azuma H, Uno Y, Shigekiyo T, Saito S. Congenital plasminogen deficiency caused by a Ser572 to Pro mutation. Blood 1993; 82: 475-480
    PubMedSearch in Google Scholar
  • 11 Hasegawa DK, Tyler BJ, Edson JR. Thrombotic disease in three families with inherited plasminogen deficiency. Blood 1982; 60 (Suppl) (Suppl. 01) 213
    PubMedSearch in Google Scholar
  • 12 Shigekiyo T, Uno Y, Tomonari A, Satoh K, Hondo H, Ueda S, Saito S. Type I congenital plasminogen deficiency is not a risk factor for thrombosis. Thromb Haemost 1992; 67: 189-192
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 McLean JW, Tomlinson JE, Kuang W-J, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM. cDNA sequence of human apolipoprotein(a) is homogeneous to plasminogen. Nature 1987; 300: 132-137
    PubMedSearch in Google Scholar
  • 14 Ichinose A. Multiple members of the plasminogen-apolipoprotein(a) gene family associated with thrombosis. Biochemistry 1992; 31: 3113-3118
    CrossrefPubMedSearch in Google Scholar
  • 15 Rodgers GM, Shuman MA. Congenital thrombotic disorders. Am J Hematol 1996; 21: 419-430
    PubMedSearch in Google Scholar
  • 16 Girolami A, Marafioti F, Rubertelli M, Cappellato MG. Congenital heterozygous plasminogen deficiency associated with a severe thrombotic tendency. Acta Haematol 1986; 75: 54-57
    CrossrefPubMedSearch in Google Scholar
  • 17 Dolan G, Greaves M, Cooper P, Preston FE. Thrombovascular disease and familial plasminogen deficiency: a report of three kindreds. Br J Haematol 1988; 70: 417-421
    CrossrefPubMedSearch in Google Scholar
  • 18 Schutta HS, Williams EC, Baranski BG, Sutula TP. Cerebral venous thrombosis with plasminogen deficiency. Stroke 1991; 22: 401-405
    CrossrefPubMedSearch in Google Scholar
  • 19 Girolami A, Sartori MT, Saggiorato G, Sgarabotto D, Patrassi GM. Symptomatic versus asymptomatic patients in congenital hypoplasminogenemia: a statistical analysis. Haematologia 1994; 26: 59-65
    PubMedSearch in Google Scholar
  • 20 Scanu AM, Lawn RM, Breg K. Lipoprotein(a) and atherosclerosis: Davis conference. Ann Intern Med 1991; 115: 209-218
    CrossrefPubMedSearch in Google Scholar
  • 21 Lane DA, Ireland H, Olds RJ, Thein SL, Perry DJ, Aiach M. Antithrombin III: A database of mutations. Thromb Haemost 1991; 66: 657-661
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Malinowski DP, Sadler JE, Davie EW. Characterization of a complementary deoxyribonucleic acid coding for human and bovine plasminogen. Biochemistry 1984; 23: 4243-4250
    CrossrefPubMedSearch in Google Scholar
  • 23 Marti T, Schaller J, Rickli EE. Determination of the complete amino acid sequence of porcine miniplasminogen. Eur J Biochem 1985; 149: 279-285
    CrossrefPubMedSearch in Google Scholar
  • 24 Gonzalez-Gronow M, Grenett HE, Fuller GM, Pizzo SV. The role of carbohydrate in the function of human plasminogen: comparison of the protein obtained from molecular cloning and expression in Escherichia coli and COS cells. Biochim Biophys Acta 1990; 1039: 269-276
    CrossrefPubMedSearch in Google Scholar