In article <4lnj1n$sl at caladan.restena.lu>, John Watson <john.watson at ci.educ.lu> writes:
|> Does X-linked hemophilia in women really exist or is a
|> double dose of the gene leathal? Is there anyone out there
|> that can give me a clear answer to this question
|>
Hello John,
In principle X inactivation is random, therefore a female carrying a mutated gene
for haemophilia is not affected. However in some cases X inactivation deviates
from randomness in a "tissue specific" manner. This is described as "lyonization"
and in these cases, a tissue may contain a much higher proportion of cells
carrying a mutated gene on the active X chromosome.
If lyonization of the factor VIII (F8) or IX (F9) genes in liver occurs, it will
result in a case of female with haemophilia.
There is a description of this phenomenon in a book called "Human Gene Mutation"
D.N. Cooper and M. Krawczak (1993) in "Human Gene Mutations" (Bios Scientific
Publishers ltd, London) pp308-309
Articles reporting cases of female haemophilia are :
Ingerslev et a., (1989). Female haemophilia A in a familiy with seeming extreme
bidirectional lyonization tendency: abnormal premature X-chromosome inactivation
? Clin. Genet. 35: 41-48
Nisen et al., (1986) The molecular basis of severe hemophilia B in a girl
N. Engl. J. Med. 315: 1139-1142
Others are also referenced in the above book chapter.
Hope this helps.
Hugues
Hugues Roest Crollius
Abt. Lehrach
Max-Planck-Institut fuer Molekulare Genetic
Ihnestrasse 73
14195 Berlin
Germany
e-mail: roest at mpimg-berlin-dahlem.mpg.de
