Re: [MLUG - DISCUSSION] Holt-Oram Syndrome

[Mike Miller <EMAIL:PROTECTED>]

On Wed, 12 Mar 2008, Jonathan King wrote:

> On Wed, Mar 12, 2008 at 9:46 AM, Mike Miller <EMAIL:PROTECTED> 
> wrote:
>
> > (2) New mutations causing dominant genetic diseases are more likely in 
> > older fathers than in younger fathers, so the 1/100,000 might increase 
> > several fold for your age group.  Nice paper on this topic:
> >
> >  http://taxa.epi.umn.edu/~mbmiller/journals/nat_rev_genet/200010_Crow_mutation.pdf
>
> Interesting reference; thanks, Mike. After I responded last night it did 
> become clear to me that a lot of cases of this disorder are apparently 
> the result of a new mutation. But just to clarify: you mean there is an 
> increased risk for all of these new mutations in older fathers, not that 
> the risk of this specific mutation (if it is one) is higher.

Exactly.  Probably all mutations increase in frequency in the sperm of 
older fathers.  We can then detect the dominant ones.  Some have been 
studied.  Not all that much is known because (A) most fathers are young 
(but that is changing) and (B) even with increased mutation rate, the 
dominant disease stay rare.


> > (3) We don't know if your son has the Holt-Oram syndrome, but even if 
> > he does have it, he might be the only one in your family.  If he does 
> > have it, *probably* half of his children would get it from him.
>
> I would say "could". I am willing to believe that by the time kids these 
> days grow up that we may have the ability to reduce these risks through 
> creative uses of genetic engineering. That would be science fiction 
> right now, though.

Actually, it isn't sci-fi now -- people are doing it.  It's called 
"preimplantation genetic diagnosis":

http://en.wikipedia.org/wiki/Preimplantation_genetic_diagnosis

Basic outline:  (1) in vitro fertilization of several ova, (2) test a cell 
for dominant disease mutation (this doesn't harm the embryo) (3) implant 
only the non-diseased embryos.  It's a little pricey right now, but it 
does work.


> > The good thing is that analysis of the TBX5 gene should answer many of 
> > your questions.  There are probably some researchers interested in 
> > whatever problem your son has and they would probably help you, at 
> > least by providing some genetic tests.
>
> Indeed. I can try to find some of these people in case they aren't so 
> easy to locate.

NIH is a great place for this kind of thing.  Coincidentally, my sister 
was just there yesterday for a follow-up on her parathyroidism and bone 
density problems.  She didn't have health insurances, but they did her 
surgery for free at NIH last year as part of a research project.

Mike

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