There are a couple of things I didn't explain very well in my previous post about the strange case of the 13-year-old girl suing a sperm bank using product liability law, on the grounds that the sperm used to conceive her carried a genetic defect resulting in her mental retardation.
First and foremost, what's with a girl inheriting Fragile X Syndrome from her father? This syndrome is (as you might expect) caused by mutations in a region located on the X chromosome, and the classic pattern of inheritance of X-linked diseases is that males are affected while females are "carriers" (who may also be affected, but usually much less severely) who can then pass the condition on to their own sons. Under this scenario the girl's story makes no sense: it seems implausible that a man with frank Fragile X Syndrome would be accepted as a sperm donor, and the girl herself should display much milder symptoms than her father.
However, the inheritance of Fragile X is more complex than the typical X-linked disorder due to the wonders of repeat expansion, which can cause the mutation to vary in severity from generation to generation. Female carriers of a severe FX mutation can indeed be cognitively affected, and some males with the mutation show a relatively mild form of the disease. Although it appears to be rare for a mildly affected male to produce a more severely affected daughter, there is at least one prior reported case of a girl affected by Fragile X inherited from a sperm donor (the linked study is in fact what triggered the girl's mother to pursue this case).
Secondly, why is the girl bringing the case forward rather than the mother? The answer appears to be that the mother tried, but failed due to the statute of limitations - a problem that doesn't apply to the daughter:
[Judge] O'Neill, however, dismissed all claims brought by her mother, Donna
Donovan, after finding that the statute of limitations had long expired
because the test done over a decade ago showed that the sperm donor was
the source of the Fragile X genetic defect in her daughter. Brittany
Donovan's claims, however, are still viable, O'Neill found, because the
Pennsylvania Minors Tolling Statute provides that the clock does not
begin to run until two years after the minor reaches the age of 18.
Anyone interested in the gory details of the case can read the judge's complete 23-page verdict here.
What puzzles me is how sperm carrying Fragile X would make it into the supply. My impression, admittedly based on anecdote, was that sperm banks operate on the basis of what can only be described as a polite flavor of eugenics. Outside of countries where the legal climate seems to be rapidly slipping toward making donors potentially responsible for paternity, it isn't that hard to find healthier than average college students willing to ejaculate for beer money. Even if no genetic testing was done, I would assume that a male with any but the mildest of Fragile X symptoms would be seen as a very undesirable donor.
Are there asymptomatic male carriers, or would the bank have had to be just that sloppy?
I an not a lawyer but it seems a legal stretch to consider sperm as a product and to define a genetic defect as a product liability issue.
If the defense succeeds does that mean the bottom feeders and ambulance chasers of the legal system can begin targeting parents with "defective" DNA for conceiving damaged offspring??
I'm not a medical geneticist, (just a lab tech. who does genetic testing, including Fragile X), but I believe the short answer to your ? about asymptomatic male carriers is, yes. In Fragile X syndrome the number of CGG repeats in the FMR1 gene is the key and with a higher number can potentially expand from one generation to the next.
Most of us have a "stable number" below 45 and do not have Fragile X. People with 45 to 55 CGG trinucleotide repeats are in a "gray zone" area. They don't have Fragile X and usually pass on a stable version to their children but are also at a slightly higher risk of having children with a higher number of repeats.
Individuals with 55 to 200 CGG repeats are in the "premutation" range and generally have few or no symptoms. People with more than 200 repeats have a "full mutation" which triggers some degree of methylation of the gene. All males with the full mutation have severe symptoms while the severity of the symptoms is decreased in females.
As mentioned in the blog post, inheritance of Fragile X is complex. More details can be found at www.fragilex.org.
The defendant is the sperm bank. They might succeed if they can show either that the daughter is not a third-party beneficiary of the contract or that they had done testing and that the sperm they provided was not from a carrier of Fragile X (almost certainly not the case, because they would have brought that up in discussions previously).
The law is fairly clear in New York that these are products. The state did exempt blood from strict liability a while ago, but, unlike Penna., they did not exempt other human tissue or transplants. Since the sperm bank is in the best position to test for genetic defects, it is reasonable to make them responsible to do so.
I had a quick look around at what some of the most popular US sperm banks screen for, in terms of their genetic testing (separate from all the other screening they do, including family history, STDs, etc).
I would have thought the genetic testing they did would have been much more extensive, but I was wrong:
California Cyrobank: http://www.cryobank.com/How-It-Works/Donor-Qualification/Genetic-Screen…
The triplet repeat expansion in Fragile X syndrome usually occurs during meiosis in the female parent. Does the affected girl have a typical full mutation triplet repeat expansion or a more rare deletion mutation? Do we know that the mother of this pateint is not a carrier of a premutation that could have expanded to a full mutation in her offspring? Does the patient have a skewed (rather than random) X inactivation pattern? If the father had a full mutation but incomplete methylation he may have had a mild phenotype. When this pathogenic mutation was passed on to the daughter it may have gained methylation, lost expression, and this X chromosome may be more prevalent as the inactivated copy in her cells (skewed X inactivation), thus providing the scenario for a more severe phenotype in the daughter. A combination of relatively rare events.