Why hemophilia is lethal for female?

[blt]

Why hemophilia is lethal (in almost 100%) for homozygotic females, while it's not lethal for hemizygotic males?

 

Both, homozygotic females and hemizygotic males don't have any healthy allel.

 

Thank you for replies

[Daecon]

At what stage of development does the lethality usually occur in females?

Edited April 19, 2017 by Daecon

[blt]

In prenatal stage, as I heard.

[John Cuthber]

How often does anyone find out?
As far as I can see you would need a haemophiliac father and a carrier mother.

That's a fairly rare combination.

Also, until fairly recently, there was a good chance that the "father" didn't survive until adulthood.

[blt]

I know it is very rare situation.

But what is the genetic reason of lethality of XhXh?

If mutation changes life-important gene at X chromosome, then XhY- should also be lethal. But it isn't. Many males live quite normally, and some of them even don't know they are sick.

 

It's easy to understand why some mutations on X chromosome are lethal for males and aren't for females. Females have second X chromosome where healthy gene exists. This rescues females lives in many recesive X-linked diseases.

 

But hemophilia is also recesive X-linked disease and situation is opposite. It's often not lethal for hemizygotic males (XhY-), where there is no chance for healthy gene, because there is no second X chromosome. It's lethal for homozygotic females (XhXh), where there is also no chance for healthy gene.

 

Why it is like that?

[Daecon]

I guess the Y chromosome is dominant and so overpowers any haemophilia effect on the X chromosome?

[blt]

The gene is on X chromosome, not on Y chromosome, so it can't be the reason.

[John S]

Here's a report on an adult female who was homozygous for hemophilia: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385172/. She suffered from the condition as expected, but it was not lethal.

And here's the abstract of another report of a homozygous adult female who had the condition but for whom it was not lethal: https://www.karger.com/Article/PDF/208614.

[jimmydasaint]

IIRC, there are about 13 factors for clotting to occur perfectly.  Heterozygotic males, namely XhY, have little  Factor VIII or IX but DO have platelets to aid clotting .  So, if I am correct, some clotting still occurs although it is imperfect. 

Edited September 17, 2017 by jimmydasaint