C9orf72 Mutation in General Population

AZ Guy

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I’ve searched the internet and can’t find the answer. Maybe someone here can help. Thank you in advance....

Is there any data out there that shows the prevalence of the C9orf72 repeat mutation in the general population or in non-ALS control groups? I’m trying to figure out if you have the mutation what the probability is that you will develop ALS in a normal life span. In other words if you get tested and find out you have the mutation is it guaranteed you will eventually get Familial ALS if you live long enough? Are there cases of people with the mutation living into their 80’s or 90’s without developing ALS? FALS is in my family so I’m 50/50.

Thanks again!
 

Nikki J

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Do you know your family carries c9?

the numbers for the general population vary widely according to location and ethnicity. It is significantly higher in Northern Europe than elsewhere . It is close to non existent in Asia.

there have been some people who say C9 isn’t as highly penetrant as previously believed but I am told at Mass General and have heard it elsewhere- penetrance approaches 100 percent by early 80s it is 50 percent by 60ish a little under 60 for males

if you are a first degree relative of someone with ALS and or FTD and have a familial pattern I strongly urge you to start participating in genetic studies. If people want answers they need to help the researchers get them. We are close for SOD1 and c9. They need carriers especially to prepare for prevention studies
 

Atsugi

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Nikki, I have question about the whole 50/50 thing.

I have been told that if a one parent has the c9 mutation, then each child has a 50/50 chance of inheriting it. I have also been told that if you inherit it, you WILL get ALS at some date.

But when I think about it, it seems to me that national medical research deals in population odds. So maybe a more accurate statement would be to say that "On average, if your parent carried the c9 mutation, then your odds of inheriting that gene are anymore from Zero to one hundred percent, with the average for all cases centered on a bell curve.

What say you?
 

lgelb

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A dominant gene has a 50/50 chance of being inherited because that is what happens with dominant genes; you get an allele from each of your parents, and the one you get from your affected parent will be either the "bad" allele s/he carries or the "good" one.

But, if you inherit a c9 mutation, research is finding that your other genes can affect what kind of disease(s) you get, in terms of combinations and severity of ALS and FTD, as well as the age of onset, as Nikki pointed out.
 

Nikki J

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What Laurie said. Now that they can do gene sequencing studies are doing that. There is an identified mutation that protects against FTD in C9. There is another gene variant that, if you have it and c9, once C9 starts you die in under a year. My neurologist has said there are surely variants that do the opposite

c9 also can present wildly differently in family members. Different diseases, different ages and different onset and progression. They are trying to figure out why
 

KimT

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Johns Hopkins routinely tests for c9, even if the patient is undiagnosed at the time of evaluation. My hope is that they're close to finding a way to block c9.
 

Atsugi

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If I walk in to Mayo in Jacksonville and say, "may I have a c9 test, please," I'll get a test. BUT, however, I want to ensure we get the best tests for all the right things.
Since Kevin Boylan retired, does anyone know the best ALS doc in Florida?

Happy to travel, too.
 

Nikki J

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If you are asking for your kids they should see a genetic counselor who knows ALS. Any provider can order the test. My pcp did mine but generally an asymptomatic possible carrier is best to have a genetic counselor who knows ALS. Unless someone can recommend one I would call the mayo clinic and ask. I know the person at mgh and she specializes in ALS and FTD but that is way out of your area. A neurologist is not the best person to counsel a potential carrier. It is different if you are symptomatic or diagnosed
 

KimT

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I’d stick with Mayo if I were looking to find answers from genetic testing. University of Florida also has genetic counselors but I’ve had some issues with them.
 

Ken15

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Since Kevin Boylan retired, does anyone know the best ALS doc in Florida?
My PALS sees Dr Oskarsson, ALS Clinic Director (Mayo, FL). She loves seeing him. As of this month, she has seen him for 2 yrs, including 5 MDC's and 14 clinical trial visits (this year alone). They are no strangers to each other.

From a caregiver's perspective, he and his staff are caring, compassionate and always doing what's best for the patient, even though limited in what can be done with this disease. One of our consolations is that, despite knowing how this movie ends, she has received the best care possible during the journey.

Ken
 

Ken15

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In other words if you get tested and find out you have the mutation is it guaranteed you will eventually get Familial ALS if you live long enough?
This appears to be a fairly recent and comprehensive study:

Age-related penetrance of the C9orf72 repeat expansion

"Our data showed that median age at symptom onset among carriers of the C9orf72 repeat expansion was 58.0 years of age (95% confidence interval: 57.0 to 59.0; see black curve in Fig. 2). The youngest reported age at symptom onset was 25 years among a man who presented with ALS. Penetrance was cumulatively nearly complete (99.5%) by 83 years of age."

Ken
 
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