Hemophilia inheritance

Hemophilia—Inherited absence of one or more of the proteins required for the blood to change from liquid to semisolid. 

DNA sequence data have been used to investigate inherited diseases such as hemophilia and muscular dystrophy, and also in cancer research. 

Deficiency of the VIIFC portion of the Factor VIII complex results in classic hemophilia or hemophilia A and is inherited as a sex-linked recessive disorder. Based on the degree of deficiency of the VIIFC molecule three different forms of hemophilia A are recognized. Less than 1% VIIFC activity equals severe hemophilia A. Two to 10% of normal VIIFC activity equals moderately severe hemophilia A. Ten to 25% of normal VIIFC activity equals minimal symptomatic disease. Deficiency of the VIIFvWFAg portion of the Factor VIII complex results in von WiUebrand disease. There are at present five principal types of von WiUebrand disease and numerous subtypes or variants. For the most part, von WiUebrand disease is inherited as an autosomal dominant, and a few subtypes may be inherited as an autosomal recessive trait. 

Congenital deficiency of Factor IX results in hemophilia B, also known as Christmas disease, and is inherited in a sex-linked recessive manner. Instmctive is the fact that some female carriers are symptomatic. Combined deficiencies of Factors VIIFC and IX have been described. 

Inherited deficiencies of the clotting system that result in bleeding are found in humans. The most common is deficiency of factor VIII, causing hemophilia A, an X chromosome-hnked disease that has played a major role in the history of the royal families of Europe. Hemophilia B is due to a deficiency of factor IX its clinical Feamres are almost identical to those of hemophilia A, but the conditions can be separated on the basis of specific assays that distinguish between the two factors. 

Von Willebrand disease (vWD) is the most common inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand factor. The disease prevalence is estimated at 30 to 100 cases per million. In contrast to hemophilia, vWD is inherited as an autosomal dominant disorder (although autosomal recessive cases exist), ensuing equal frequency in male and females.16... 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

Females have two X chromosomes, so they must inherit two copies of the mutated chromosome to develop hemophilia A. Gene frequencies are similar in males and females, so we can use the gene frequency estimated in males to predict the genotype frequencies in females. Assuming Hardy-Weinberg equilibrium, the frequency of affected females is given by... 

In the early 1980s, the development of HIV/AIDS in young blood transfusion patients was a powerful incentive to find other sources for the blood-derived proteins used to treat hemophilia, a group of inherited disorders affecting the clotting of blood. Hemophilia has... 

The hemophilias are a group of related, usually inherited, bleeding disorders. Inherited bleeding disorders include abnormalities of coagulation factors as well as platelet function. When the term hemo-... 

Factor IX (Christmas factor) is next in the intrinsic mechanism cascade. It can be activated either by XIa or by Vila of the tissue factor pathway. The absence of a functional factor IX leads to the inherited X-linked bleeding disorder hemophilia B which affects 1 in 30,000 males. The condition can be mild or very serious551552 and may be caused by a variety of mutations or by incorrect splicing of the messenger RNA for the 416-residue factor IX. The level of factor IX in blood increases with age, almost doubling by old age.552a... 

Pedigree Analysis, an approach widely used where experimental breeding is not practical. Pedigrees show the inheritance of specific Iraits. which can be traced, in all of lhe members of a family line. Human pedigrees have been very useful in terms of tracing the familial aspects of certain diseases. One of the first diseases so traced was hemophilia. Stock... 

Classical studies of the recessive, sex-linked disorder hemophilia provided evidence that a gene concerned with the synthesis of factor VIII must be situated on the X-chromosome. When it was discovered that a reduction in factor VIII was commonly present also in von WUlebrand s disease, with a somatic dominant inheritance, it became clear that another gene, on an autosome, must also be involved. Cross-transfusion experiments between patients suffering from hemophilia and von Willebrand s disease show-ed that hemophilic blood would stimulate factor VIII synthesis in von Willebrand s disease, but not vice versa. These data have made it possible to construct a number of alternative genetic models now being submitted to critical experimentation. 

B7. Bulloch, W., and Fildes, P., Hemophilia. In Treasury of Human Inheritance (Eugenics Laboratory Memoirs XII). Parts V-VI, Dulau Co., London, 1911. 

Initially, the focus of gene therapy was for the treatment of inherited disorders such as cystic fibrosis, sickle cell anemia, hemophilia, and adenosine deaminase deficiency. Gene therapy trials were later expanded to include patients with acquired diseases such as cancer and heart disease. 

Hemophilia is an inherited bleeding disorder resulting from a congenital deficiency in factor VIII or IX. 

The most common congenital bleeding disorder, von WiUebrand disease has a prevalence of 1 % to 2%. It refers to a family of disorders caused by a quantitative and/or qualitative defect of von WiUebrand factor, a glycoprotein that plays a role in both platelet aggregation and coagulation. Unlike hemophilia, von WiUebrand disease has an autosomal inheritance pattern, resulting in an equal frequency of disease in males and females. 

Clinically, disorders of Factor VIII are the most common inherited abnormalities of hemostasis. Classical hemophilia A, Factor VIII deficiency, occurs in approximately 1 out of 20,000 live births in the United States. 

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