The researcher Dr. Michael Hayden has published the latest studies regarding CAG. Marsha provides a synopsis of his published work on the HDlighthouse at [www.hdlighthouse.org].

Steve Ireland



Edited 1 time(s). Last edit at 09/18/2006 09:19PM by stevei.

Steve,

Thanks for alerting us to this information.

Marsha,

Thank you for the review of the article. It was very useful.

Those who have reduced penetrance: what exactly does that term mean? Some brain cells are spared? They are just as mean as the others according to our family history about my GGrandmother.

Reduced penetrance means that, in this case, HD may or may not express itself, as the gene at those CAG counts is not a fully dominate gene...At a CAG of 40 and over it will behave like a fully dominate gene and one will see HD symptoms during course of a full life. When it does express itself at the lower CAG's it may behave just as it does at the higher CAG's. Penetrace has no correlation to what symptoms will be if they happen at a lower CAG.

CAG at 40 and up= full penetrance or in other you would show symptoms at some point

CAG at 36-39 = reduced penetrance or you may or may not show symptoms

CAG of 27-35 = no symptoms but may pass an expanded copy to offspring

CAG 26 and below _ normal, no definition for normal but it sounds fun huh?

that is what they say. But the number of persons with the 35-39 level CAG is so small and many have lived and died without being studied before the genetic testing was available. No clinical histories of depression or bipolar are collected because the connection is not recognized.
I think this report contains too many assumptions about what reduced penetrance actually means.

I would guess that the figures are fairly accurate based on the data and what the clinical definition of symptoms is. The figures could change if a person suffering chronic depression at age 60 with a CAG of 38 could be be proven that depression was a direct cause of the HD gene. Even so I don't think this is that far off one way or the other. There are people with those CAGs at between 36-39 who never show symptoms. That will always make those CAG counts reduced penetrance. The percentage of those who they find with symptoms may fluctuate...but it will never be all of those people like it is at 40 and above.

why? why the sudden difference?

how many in the groups that give them these numbers...we might only be talking about a few cases in the reduced penetrance range.

It doesn't matter. Anything less than 100% certainty of HD symptoms is reduced. That is all it is saying. That is all it ever was saying.

The data in the Hayden report isn't just based on his own clinic. He's including data from other studies as well. I know that there were 80 people in the last Venezuela study who fell within the reduced penetrance range so I would think that we are talking about more than a just a few people.

I know someone whose grandfather in law had 39 repeats and lived to be 90 without any signs of of HD, physical or cognitive or psychiatric. He's famous in the literature.

If by "Why the sudden difference" you mean why should some people stay healthy at 39 while virtually everyone at 40 gets sick eventually (I say virtually because there's a handful of cases of people with 40-42 repeats living to old age without symptoms), well I think you have to look at other factors. There are other genes which affect age of onset. Most of them aren't known but can be assumed because of kinship studies. Environmental factors play a part too. It could be that inheriting genes which delay onset and a healthy anti-aging lifestyle makes the difference for some in the reduced penetrance range.

The way a lot of the researchers look at this, the alleles with 36-39 counts ARE HD genes and if people lived long enough, closer to the upper possibility of the life span (which I believe is 120), those in that range would develop HD too.

Cellular energy is precisely correlated with the CAG count of the highest allele. The higher the number, the less energy available in the cell. Once you get to 40 repeats, the cell is significantly challenged and symptoms develop over time as coping mechanisms fail. It just seems to make sense to me that we'd see individual variation even at the same CAG repeat number just as we see some individuals aging with better health than others.



Edited 1 time(s). Last edit at 09/25/2006 01:29PM by Marsha.

I went back and read the Venezuela study again. None of those 80 people they've been studying with intermediate alleles have developed Huntington's Disease as yet. They are using the classic, neurological definition.

Here's something else which was mentioned which I found interesting: "The Venezuelans' average age of onset is 34.35 (? 10.07) years in contrast to the mean age of onset for Americans (37.47 ? 13.28) and Canadians (40.36 ? 12.97)"

Here's the study:
[www.pubmedcentral.nih.gov]

So in otherwords cold is good?

Or perhaps universal health care is good.

I must be one of the few cases. My CAG is 38 with reduced penetrance.I have been symptomatic for a few years, since 2000. I'm 63 years old now.


My daughter has 37 repeats with reduced penetrance. She is 47 years old and has started her onset. We are both seen at the Center of Excellence in Columbus, Oh. I have 7 siblings whom have not been tested. Head in sand for the boys, the other 3 girls are considering being tested.

HD has caused a family fued..............Some supporters but most are in deniel. Mom is in very late stages but she is in deniel









God Bless, Pray for a cure.

Just Me.

Mine is cheaper...lol. What is the average age of onset in UK, France,and Australia? That would even up the pool and at least they would represent less trouble plagued healthcare systems. Need more numbers or I am going with freezer therapy.

So, i've only read this thread a bit. I wonder if the countries with the higher age of onset, like Canada, does Canada also have a higher life expectancy for the whole population, nothing to do with hd, just in general? And do the countries with lower age of onset, also have lower life expectancy in general, for their population?, non hd related?

Ok, although i had trouble reading the venezuela link, i was able to read some of the summaries. And it says that in the average population of venezuela, there is not a low life expectancy, in the general population.

K, now, this is real cool, life expectancy chart for different countries, straight from the CIA!

[www.cia.gov]

Barb, thanks for posting that link, it is very cool. And it is just the kind of thing that we genealogists can chew over and attempt to draw some conclusions. I'm grateful.

I believe my moms CAG is 39 . She certainly does not have a severe case of HD compared to others . Her last MRI did show significant deterioration from the previous one just 3 years before . My mom is about 78 her mom died at almost 94 . My uncle on my dads side was 79 I think when he died and he had HD . My cousin an older cousin must be in her early 70s and is still alive although she is in a nursing home , but she still can use a walker and has some good days . I think that people with lower CAGs do live longer and symptoms are not as bad , but from where I stand they do get the disease . All my best. db

I am 49 years old, with a CAG of 39, i became symptomatic 4 years ago. My Dad is 74 years old, and his CAG is 39, and he became symptomatic just over a year ago. My Dad was told that people like him having such a late onset, that even though he is symptomatic, he probably will not go into really late stage hd, but he will probably die from old age related illness, and that his symptoms may be less. But, it has to do with his age, not his CAG, because when i was diagnosed, at age 46, as being in the early stages, i asked, with my CAG being 39, does that mean i will have less severe hd. They said the biggest factor is not the CAG, but the age of onset. The older you are, the slower and less severe the course of the illness, is what i was told by my neurologist. The younger, the faster and more severe the illness is.



Edited 3 time(s). Last edit at 09/25/2006 10:56PM by Barb.