children whose parents don't have BPES (explanation)

[Guest guest]

Hi all

From this site I have copied some text and put it below.

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

Recently there have been some posts relating to the very rare situation where two parents, neither of whom have BPES, have more than one child with BPES.

If you take a look at the text below - the 3rd and 4th points under "Sibs of proband" has explanations relevant to this situation.

It would be inappropriate for me to try and explain this in any further detail because I don't have the right background and I am qualified to do so. Perhaps one of the members of this group who are doctors might be able to help out here.

I am not sure how long this information has been available. From what I have been able to deduce by looking that the dates of the articles, it looks like the information has been added to the site at the start of the year.

Shireen Mohandes

London, England

Risk to Family Members

Parents of a proband

Some individuals diagnosed with BPES have an affected parent. A proband with BPES may have the disorder as the result of a de novo gene mutation. The proportion of cases caused by de novo mutations is estimated at more than 50% [unpublished data]. Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include molecular genetic testing of the FOXL2 gene if a mutation has been identified in the proband and clinical examination for subtle features of BPES.

Note: Variable expressivity of BPES features has only been reported in mosaic cases [unpublished data].

Sibs of a proband

The risk to the sibs of the proband depends upon the genetic status of the proband's parents.

If a parent of the proband is affected, the risk to the sibs is 50%.

When the parents are clinically unaffected and do not have a FOXL2 mutation, the risk to the sibs of a proband appears to be low.

If a disease-causing FOXL2 mutation cannot be detected in the DNA of either parent, two possible explanations are germline mosaicism in a parent or a de novo mutation in the proband. The risk to the sibs of the proband depends on the probability of germline mosaicism in a parent of the proband and the spontaneous mutation rate of FOXL2. Germline mosaicism has been observed in BPES and demonstrated at the molecular level [beysen et al 2005]; its incidence is unknown.

Offspring of a proband. Each child of an individual with BPES has a 50% chance of inheriting the mutation.

Other family members of a proband. The risk to other family members depends upon the genetic status of the proband's parents. If a parent is found to be affected, his or her family members are at risk.