Genetics - 2 good things to read

[Guest guest]

From Shireen, in London, England

Dear members of the group, especially new members.

With apologies to people who have been a member of this group

for a while, I am posting, again, 2 very useful pieces of information for the new

members of the group. The first is an article written by the people who work at

the lab in Belgium (Dr De Beare, and Dr Beysen) who are leading the research on

BPES. The second is a very understandable email from Jeroen – who has spoken

to Dr De Beare about himself and his family, and being a medic, he is able to explain

things accurately but in simpler terms for us non-medics.

Lab in Belgium who carries out tests are the same as the authors

of this article:

Please click here to read the article (which is quite technical

and not always understandable)

http://www.geneclinics.org/servlet/access?db=geneclinics & site=gt & id=8888891 & key=yvyThuThGZXK5 & gry= & fcn=y & fw=suti & filename=/profiles/bpes/index.html

Author

Information

Diane Beysen, MD , Center for Medical Genetics

Elfride De Baere, MD, PhD , Center for Medical Genetics

Ghent University Hospital, Ghent, Belgium

Here

is some info about Dr Elfride De Beare and how to get in touch with her

http://medgen.ugent.be/CMGG/medewerkers.php?user_id=7

Post from Jeroen (who is in the medical profession) about BPES and

fertility

> Sent: 11 November 2005 14:13

> blepharophimosis

> Subject: blepharophimosis Type I or

type II? Recent developments.

>

> Hi everybody,

>

> I read the recent posts about type I and type II BPES and

> infertility. I noticed that there are a lot of questions and

> uncertainties. Maybe I can clarify one and other. I have a

> degree in medicine and although I am now specializing in

> psychiatry, I am familiar with general medicine matters.

> Moreover, recently I spoke with Dr. Debaere, who's a world

> expert on genetic research in BPES.

>

> First I'd like to explain something about genetics. Humans

> have 46 chromosomes. We have 2 Sex chromosomes, XX (female)

> or XY (male), and 44 autosomal chromosomes. Each parent

> Passes 23 chromosomes (22 autosomal and 1 sex chromosome) so

> you get 23 chromosome " couples " .

> Chromosomes consist of DNA. Specific regions on chromosomes

> are called genes. There are a lot of genes (eye-colour,

> hair-colour, ...

> etc). In our cells there is a sophisticated system that can

> translate the information which is encoded in the DNA, the

> building material of genes, and form proteins. So a gene

> actually stands for a specific protein (like there is a gene

> for insulin). How do genetic disorders arise? Genetic

> disorders arise when there is a mutation (change) in the DNA

> within a specific gene region. This alters the gene and,

> thus, alters the protein which is formed. This is important.

> For example insulin which is different from normal insulin

> might not be able to lower blood sugar levels. Once a genetic

> disorder has arisen, which can happen spontaneously, it can

> be passed from parents to children. Genetic disorders can be

> " dominant " or " recessive " . When a genetic disorder is

> dominant only one of the two genes in the gene couple (the

> one from father or the one from mother) has to be altered to

> give rise to the disorder.

> When a genetic disorder is recessive both the father and the

> mother need to pass an altered gene to give rise to the disorder.

>

> What about BPES? BPES is an autosomal dominant genetic

> disorder. The gene is called FOXL2 and is located on

> chromosome 3. Chromosome 3 is an autosomal chromosome and the

> fact that the disorder is dominant means that you only need

> to have one altered gene to get the disorder. The different

> types (I and II) of BPES were first described in 1983

> (Zlotogora). Type I includes the four major features

> (blepharophimosis, ptosis, epicanthus inversus and

> telecanthus) and female infertility caused by premature

> ovarian failure (POF). Type II includes only the four major

> features. The difference between Type I and II is the

> position on which the DNA, and thus the gene, is mutated

> (altered). There are several (at least

> 21) known mutations of the FOXL2 gene. Depending on the

> location these mutations give rise to a shortened protein or

> an extended protein. The ones that give rise to a shortened

> protein cause type I and the ones that give rise to an

> extended protein cause type II.

> For some mutations it's not clear which type they cause.

> During a genetic investigation, which takes about three

> months, they try to find a known mutation to see if they are

> able to tell which type of BPES the affected person has.

>

> What about the management of POF? Management of POF needs to

> address the two major medical issues: hormone replacement

> therapy (HRT) and infertility.

>

> HRT: Oestrogen and progesterone replacement therapy is

> usually indicated. No comparative data are available to guide

> estrogen use in young women as most studies on HRT involve

> post-menopausal women, but the advantages often outweigh the

> possible side-effects.

>

> Infertility: No effective treatment for infertility exists.

> Adoption and oocyte (egg) donation are among the available

> options. However, more recently there are some new therapies

> under investigation.

> Ovarian tissue and oocyte cryopreservation (freezing in) hold

> promise for fertility preservation in the women most likely

> to undergo ovarian failure. Adolescent girls with BPES who

> have a risk of developing POF could be candidates for ovarian

> (not necessarily the complete ovary so it's not necessary to

> cause surgical

> menopause) cryopreservation. This cryopreserved ovarian

> tissue can be used in two ways: retransplanting and in vitro

> stimulation. The first live birth after retransplantation was

> reported in 2004 (this was not a woman with BPES). Note that

> these techniques are not (yet) applied on a large scale.

> Women with POF often reach menopause when they are 25-30 years old.

> In the old days, when women conceived at a younger age, this

> was not necessarily a problem. Nowadays most women start a

> career and think of children at an older age which makes POF

> more of an issue.

> Endocrinologic and gynecologic follow-up are advised in

> affected females in whom the BPES type is unknown or in whom

> BPES type I is suspected based on a positive family history

> or suggestive FOXL2 mutation.

>

> I myself had a blood sample taken one and a half month ago.

> We are planning to have more kids and we just want to know

> which type I have to be as prepared ad possible. I do not

> have the result yet. It takes about three months.

>

> I hope I was of any help. If some things are unclear please

> ask questions.

>

> Greetings,

> Jeroen.