When I first found out about
III's chromosome inversion, but before we saw the doctor, I went to goo.
gle to try to find either information or others who had discussed in their blogs a similar situation. It's such a technical thing... so it was hard to find anything, or when I did I didn't understand it. So, one of the things I've been wanting to do is to give some more technical information about our inversion
as I understand it so that if there are others who have a similar situation, they are able to get some info from our situation.
My disclaimer is that I am not a scientist; I am not a doctor. What I have posted here is a combination of what I remember the geneticist sharing with us, what she sent in her letter to my RE, and what I've found myself on goo.
gle based on what she told us. Don't take my information as "the word". All I can tell you is what is true, based on my own elementary understanding, in
our situation.
My first goo.
gle search, before our genetic counseling session, resulted in this find. It is written for the layperson, so I found it helpful and informative:
PGD for patients that are carriers of chromosomal translocations
This is another rare situation in which a couple knows that one of them has a chromosomal arrangement called a balanced translocation. When someone (the husband or the wife) has a balanced chromosomal translocation they are normal - until they try to have a child. When their chromosomes join with those of their partner in the fertilized egg they make a high percentage of chromosomally abnormal embryos.
These embryos are at very high risk for miscarriage or could result in the birth of a child with birth defects. This is another situation where PGD can help. By having IVF and PGD, they can have chromosomally normal embryos transferred (if there are any) - greatly reducing their risk for miscarriage and birth defects.
PGD for aneuploidy screening (PGS) - checking the chromosomes (because they are having IVF and the wife is 38 or older, or because of multiple previous IVF failures)
Background: Human eggs are often chromosomally abnormal - and the percentage of eggs with a chromosomal abnormality increases with increasing female age. In general, it seems that about 25-40% of human embryos have some type of chromosomal abnormality. This increases to about 50% and higher as women approach or exceed age 40.
Theory: By testing the chromosomes of the embryos available for transfer, we can discard all embryos with abnormal chromosomal arrangements and pick the embryo(s) for transfer to the wife's uterus from those demonstrating normal chromosomes. This is fascinating technology, and the theory is logical as well. However, the data from studies on pregnancy outcomes after PGD testing of chromosomal normality does not appear to show any clear benefit at this time.PGD for aneuploidy is often referred to as preimplantation genetic screening, or PGS (instead of diagnosis).
http://www.advancedfertility.com/preimplantation_genetic_diagnosis.htm
III has an inversion, also called a "chromosomal
translocation"*, of his chromosome 2. It is at the spot p23,q23. I don't really understand what that means- just that it's the location on the chromosome. It is a "
pericentric inversion" which means it includes the center part of the chromosome (our geneticist called it the "waist"). So basically what that means is that part of the chromosome is flipped over.
During "meiosis" (the process which creates the sperm), each chromosome pair actually lines up and exchanges genes from one to the other. (So one half of the ch.2 exchanges genes with it's matching half.) Then they separate and one goes to one sperm, and the other goes to another sperm. When they line up, if there is an inversion, the chromosomes can loop around allowing the crossover to be balanced. There is also the possibility of an unbalanced crossover if they do not line up correctly.
The geneticist showed us a very basic picture of what that means. The first is what a normal person's chromosomes would look like- except I've drawn in red lines where the inversion might occur. The second picture is with the inversion. The last two are examples of what
could result during meiosis.
Each person has 23 pairs of chromosomes. Through the process of conception, a potential fetus gets one chromosome from each pair from each parents. (The s.ex chromosomes are an easy explanation of this- a baby gets one of the mother's two x chromosomes, and then either the father's x chromosome or his y chromosome, determining what gender the baby will be.)
III's translocation only affects one of the chromosomes in the 2
nd pair.
Some good things:
- Of III's pair of chromosome 2, one is normal. The process by which the pair is distributed to his sperm (each sperm carries one of each pair of each chromosome) is totally random. So it is possible to have sperm that are unaffected by the inversion.
- Our geneticist told us III's is "rather large" inversion. The larger the section that is inverted, the more able it is to correct itself during conception.
- Through the non-inverted ch.2 and through an inverted ch.2 that corrects itself during alignment (I don't know if that's the correct term), we could have a totally normal embryo.
Some negatives:
- If an embryo is affected by the inversion, it could result in a miscarriage, in a baby with birth defects (though the severity is unpredictable), or it may not implant at all.
- With "natural fertilization" there may be a lower incidence of having an embryo affected by the inversion since the sperm would likely be slower/less efficient swimmers. Since we have fertilization issues (possibly caused by the inversion), we have to do ICSI, increasing the chances of an embryo being affected.
Below is more information I found through Dr. Goo.
gle. It's pretty technical, but explains the
occurrence of the chromosome "fixing" itself and has a pretty good picture of that.
Inversions involve two chromosomal breaks and rejoining, with the broken piece reincorporated in the opposite orientation from which it naturally occurs. When they include the centromere, they are called pericentric inversions... inversions arise in mitotic cells. If they arise in precursors of the gametes, they may produce abnormal genomes as they progress through meiosis. Recombination between homologous chromosomes is a necessary part of every normal meiosis. The probability for nondisjunction is greatly increased if there is no recombination. However, recombination between a chromosome with an inversion and its normal homolog may result in two abnormal chromosomes being produced. ...four different gametic products are produced, one normal, one has the inversion, and two have duplicated portions and deleted portions. The effect on the phenotype is almost always deleterious, but the magnitude of the effect depends upon the size of the duplications and deletions, and where they occur.
http://www.uic.edu/classes/bms/bms655/lesson10.htmlThis picture from the above link shows the meiosis process and the different ways the pairs can crossover.
Another, more technical, picture.
I hope this information is useful, or at least interesting, to someone. We have decided to use PGD, and feel our clinic is experienced in this process. Clearly, I'll keep you all updated about how it goes. ;)
*ETA: After reading Julia's post on balanced translocation and then doing a little goo.gle research myself, I wanted to clarify. While the geneticist used the term "chromosomal translocation", much of what is on the internet describes something different than what has happened with us. III's inversion only involves one chromosome, as opposed to a "reciprocal translocation" or a "Robertsonian translocations". In each of those, there are 2 different chromosomes involved. III's translocation is within only one chromosome.
