Editing Hemophilia A

==Hemophilia A==

===General background information===

===Mode of inheritance===
*'''X-linked recessive'''


===Single important gene===
*The FVIII gene makes the clotting cascade enzyme Factor VIII.
*The gene is large: 186 kb with 26 exons.

===Etiology===
*There are a variety of mutations and mutation types (large / small deletions, insertions, missense, etc.) that cause hemophilia A.
**Large or small deletions, insertions,  missense, etc.
**We will use Hemophilia A specifically as '''an example of unusual crossing over'''.
***Occurs in 40-50% of Hemophilia A cases


*Unusual crossing over:
**In hemophilia A, an inversion within the gene arising from crossing over causes disruption of the gene.
**'''The inversion in Hemophilia A usually occurs during male meiosis'''.
**Recall that exons are numbered for their position (starting with 1) as one moves in the direction of transcription.
**The wild-type order is 1->26.
**There are, however, inverted repeats downstream of the first exon and upstream of the 22nd exon that can pair to allow inversion.
**The inversion flips exons 1-22 over, leaving the final order 22->...->1->23->...->26

===Pathogenesis===
*Pts with > 25% function of factor VIII of the clotting cascade will have no symptoms.
**As the amount of factor VIII function approaches 5% of normal, symptoms begin to manifest.
**< 1% factor VIII function manifests severe disease: frequent bleeding (even spontaneously), bleeding into joints

===Phenotypic information===
*External bleeding episodes
*Prolonged bleeding from a circumcision wound or a venepuncture or heelprick is another common early sign of haemophilia
*Prolonged bleeding from common injuries, or in severe cases bleeds may be spontaneous and without obvious cause.
*The most serious sites of bleeding are: joints, muscles, digestive tract, and brain
**The muscle and joint haemorrhages are indicative of haemophilia
**Digestive tract and cerebral haemorrhages are also germane to other coagulation disorders
*Repeated bleeds into a joint capsule can cause permanent joint damage and disfigurement resulting in chronic arthritis and disability.
**Joint damage is not a result of blood in the capsule but rather the healing process.
**When blood in the joint is broken down by enzymes in the body, the bone in that area is also degraded.

===Diagnosis===

===Treatment===

===Recent research===

===5 important facts===

===Not to be confused with===

===Questions and answers===