Inherited diseases hemophilia

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

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. 

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... 

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. 

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. 

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. 

Sloe Klotter has hemophilia A, the most frequently encountered serious ] disorder of blood coagulation in humans, occurring in 1 in every 10,000 males. The disease is transmitted with an X-linked pattern of inheritance. 

The mode of inheritance of numerous human diseases is similar to that just described for the sex-linked trait in Drosophila. Two diseases are most typical in this respect—color blindness and hemophilia. Color blindness is a rather common disease, but the distribution among male and female varies considerably. The... 

Von Willebrand s disease was at first thought to result from a failure of capillary function. Later it was demonstrated that patients affected by this disease lack antihemophilic globulin, which explains the new name for the disease—vascular hemophilia. The condition seems to be inherited as an autosomal dominant trait. It is not known whether the capillary deficiency and the deficiency in antihemophilic globulin are inherited simultaneously or separately. Other combined deficiencies have been described in very few patients. Some examples of combined deficiencies are deficiency of AHF and PTC, AHF and factor V, PTC and SPCA (these situations are rare and sometimes very difficult to describe), and AHF and PTA. 

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