Other Free Encyclopedias » Medicine Encyclopedia » Genetics in Medicine - Part 2

Hemophilia - Gene Defects Causing Hemophilia, Detection Of Fviii Or Fix Gene Defect In Family: Carrier Detection

chromosome genetic chromosome males daughters normal

Hemophilia A and hemophilia B are genetic disorders in the blood-clotting system, characterized by bleeding into joints and soft tissues, and by excessive bleeding into any site experiencing trauma or undergoing surgery. Hemophilia A and B are clinically indistinguishable. Both have the same type of bleeding manifestations, and both affect males almost exclusively. The coagulation cascade involves multistep conversion of several factors into their active (A) forms. In hemophilia, factors VIII or IX are missing or present in insufficient amounts. The two conditions can be distinguished by detecting the responsible defective proteins.

Contrary to popular belief, individuals with hemophilia rarely bleed excessively from minor cuts or scratches. Hemophilia A and B are both worldwide in distribution, affecting all racial and ethnic groups. The prevalence of hemophilia A is approximately 1 in 10,000 males, and that of hemophilia B is 1 in 30,000 males.

The disorder was recognized (although not named) in Babylonian times. A second-century Jewish rabbi gave permission for a woman not to have her third son circumcised after her first two sons died from the procedure. No doubt the most famous carrier of hemophilia was the nineteenth-century Queen Victoria, whose son, Prince Leopold, had the disorder, and whose two daughters inherited and passed on the gene. Ultimately several of the European royal families were affected by Queen Victoria's gene.

There are a number of clotting factors that interact to form a stable blood clot following injury or surgery. Each factor has a name and is produced in certain cells (usually in the liver), encoded by a certain gene. Hemophilia is caused by a defect in one of these genes. In the case of hemophilia A, factor VIII (FVIII) is deficient or absent. In hemophilia B, FIX is deficient in amount or absent, or it does not function properly.

The genes encoding FVIII and FIX are on the long arm of the X chromosome. Because males have only one X chromosome, hemophilia A and hemophilia B affect males almost exclusively. If a boy's X chromosome has the defective gene that causes hemophilia A or B, the boy will have hemophilia.

Since boys with hemophilia have only an X chromosome carrying the defective gene that causes hemophilia A or B, and no gene for the production of normal FVIII (or FIX), and since fathers pass an X chromosome on to their daughters, all of their daughters will be "obligate carriers" for hemophilia. Obligate carriers—individuals who are definitely carriers—include daughters of men with hemophilia and women who have a maternal family history of hemophilia and one or more affected sons or grandsons.

In general, such carrier females do not bleed excessively, as their other X chromosome, with a gene for normal FVIII (or FIX) production, results in intermediate levels of FVIII (or FIX). However, carrier females have a fifty-fifty chance of passing their X chromosome that bears the hemophilia gene to each child they might have. A son would have an equal chance of being normal or having hemophilia. A girl would have an equal chance of being normal or being a carrier, like her mother.

Heterozygote Advantage - Agricultural Significance, Hypotheses Of Heterozygote Advantage, Heterozygote Superiority In Humans [next] [back] Hemoglobinopathies - Hemoglobin Structure And Function, The Genetics Of Hemoglobinopathies, Sickle Cell Disease, Treatment Options And Continuing Research

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