Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Autosomal dominanter Protein C-Mangel

Der autosomal dominante Protein C-Mangel wird durch Mutationen im PROC-Gen hervorgerufen. Im Unterschied zur rezessiven Form liegt hier eine so schwerwiegende Mutation vor, so dass ein einzelnes mutiertes Allel eine Thrombophilie auslösen kann.

Einteilung

Klinisch chemisch werden drei Typen des Protein S-Mangels unterschieden: Typ 1: Es liegt sowohl eine Mangel an nachweisbarem Protein und seiner Aktivität vor. Typ 2: Während die Proteinkonzentration normal ist, zeigt die Aktivität des reifen Proteins eine deutliche Verminderung.[1]

Diagnosestellung

Bei der Plasmabestimmung sollte man beachten, dass diese Protein Vitamin K-abhängig gebildet wird, also eine längere MArcumar-Pause vor der Abnahme erforderlich ist.

Gliederung

Venöse thromboembolische Erkrankungen
Autosomal dominanter Protein C-Mangel
PROC
Autosomal dominanter Protein S-Mangel
Autosomal rezessiver Protein C-Mangel
Autosomal rezessiver Protein S-Mangel
F2
F5
Faktor XII-Mangel
HABP2
MTHFR
PAI-Transkriptionsmodulator
Protein Z-Mangel
SERPINC1
THBD
VKORC1

Referenzen:

1.

Debus O et al. (1998) Factor V Leiden and genetic defects of thrombophilia in childhood porencephaly.

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2.

Millar DS et al. (2000) Molecular genetic analysis of severe protein C deficiency.

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3.

Gruppo R et al. (2000) Protein C deficiency related to valproic acid therapy: a possible association with childhood stroke.

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4.

Lay AJ et al. (2005) Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities.

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5.

Iijima K et al. (1991) A new hereditary abnormal protein C (protein C Yonago) with a dysfunctional Gla-domain.

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6.

Romeo G et al. (1987) Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene.

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7.

Bovill EG et al. (1989) The clinical spectrum of heterozygous protein C deficiency in a large New England kindred.

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8.

Israels SJ et al. (1987) Childhood stroke associated with protein C or S deficiency.

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9.

Clouse LH et al. (1986) The regulation of hemostasis: the protein C system.

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10.

Conlan MG et al. (1988) Familial type II protein C deficiency associated with warfarin-induced skin necrosis and bilateral adrenal hemorrhage.

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11.

Rocchi M et al. (1986) Mapping through somatic cell hybrids and cDNA probes of protein C to chromosome 2, factor X to chromosome 13, and alpha 1-acid glycoprotein to chromosome 9.

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12.

Mitchell CA et al. (1987) A fatal thrombotic disorder associated with an acquired inhibitor of protein C.

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13.

Pabinger I et al. (1986) Coumarin induced acral skin necrosis associated with hereditary protein C deficiency.

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14.

Mibashan RS et al. (1985) Prenatal diagnosis of hereditary protein C deficiency.

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15.

Pabinger-Fasching I et al. (1985) Protein C deficiency in Austria.

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16.

Mannucci PM et al. (1982) Deficiencies of protein C, an inhibitor of blood coagulation.

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17.

Barbui T et al. (1984) Hereditary dysfunctional protein C (protein C Bergamo) and thrombosis.

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18.

Bertina RM et al. (1984) The use of a functional and immunologic assay for plasma protein C in the study of the heterogeneity of congenital protein C deficiency.

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19.

Pabinger-Fasching I et al. (1983) Protein C deficiency in two Austrian families.

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20.

Broekmans AW et al. (1983) Congenital protein C deficiency and venous thromboembolism. A study of three Dutch families.

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21.

Griffin JH et al. (1981) Deficiency of protein C in congenital thrombotic disease.

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22.

Bertina RM et al. (1982) Protein C deficiency in a Dutch family with thrombotic disease.

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23.

Reitsma PH et al. (1995) Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH.

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24.

Hallam PJ et al. (1995) Population differences in the frequency of the factor V Leiden variant among people with clinically symptomatic protein C deficiency.

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25.

Gandrille S et al. (1995) Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM.

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26.

Glueck CJ et al. (1994) Protein C and S deficiency, thrombophilia, and hypofibrinolysis: pathophysiologic causes of Legg-Perthes disease.

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27.

Koeleman BP et al. (1994) Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.

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28.

Allaart CF et al. (1993) Increased risk of venous thrombosis in carriers of hereditary protein C deficiency defect.

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29.

Berdeaux DH et al. (1993) Dysfunctional protein C deficiency (type II). A report of 11 cases in 3 American families and review of the literature.

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30.

Reitsma PH et al. (1993) Protein C deficiency: a database of mutations. For the Protein C & S Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.

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31.

Reitsma PH et al. (1996) Protein C deficiency: summary of the 1995 database update.

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