The gene for factor VIII is located on the X chromosome (locus Xq28) and is 186,000 bp long (0.1% of the entire X chromosome) and contains 26 exons. The protein encoded by this gene is composed of 2351 amino acids with a total relative mass of 267 039 daltons (Figure 2).
The location of the factor VIII gene on the gonosome (X chromosome) determines the recessive mode of inheritance of the disease. Women are very rarely affected, and most often have a carrier state, i.e. the presence of a single mutated allele that they can pass on to their offspring. Only boys are affected; rarely, a female haemophiliac may be affected if her father was a haemophiliac and her mother a carrier.
As a practical matter, it is essential that all the sons of a haemophiliac be healthy and all his daughters be carriers. 50% of the sons of a carrier mother will be healthy and 50% will have haemophilia. Half of their daughters may also be carriers and half will be healthy women.
About 20-30% of hemophiliacs have a negative family history. In this case, either the mutation is newly acquired or the disability has been passed down for generations only by female carriers, without clinical manifestations of the disease.
The manifestations of haemophilia, i.e. the extent of the disability and the history and clinical course of the disease, as well as the factor level, are a direct expression of the genetic disability and tend to be the same in members of the same family. The disease occurs worldwide and no racial dependence has been found.
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