My Heart, My Family, and MYBPC3

By Arnab Chowdry, Senior Scientific Software Engineer at 23andMe

Having been young and healthy for the majority of my life, I haven’t had many opportunities to interact with our health care system.  Not too long ago I was a sedentary, slightly-overweight, South Asian man entering my thirties.  I had some ambiguous family history of diabetes but, like everyone I know, I felt that the less I saw my doctor, the better.  Most importantly, by medical standards, I had no reason to consider myself predisposed to heart disease.

Then, not long ago, my 23andMe data and a paper in Nature Genetics changed my story.  Ironically, I work for 23andMe as a scientist and engineer; I analyze genetic data for a living, but until then my work had been abstract.  I knew we were helping people but never expected any particularly life-altering information to come out of my personal genetics.

It turns out that I carry a mutation in the MYBPC3 gene that is associated with familial hypertrophic cardiomyopathy (HCM). South Asians that carry this mutation are at greatly increased risk for HCM.  Well that’s strange–if I’m a carrier, then one of my parents has to be a carrier, and one of their parents (and so on).  But if it is such a significant modifier of risk, shouldn’t I have heard of HCM running in my family, before?

With some research, I learned that HCM is not commonly screened for, in the United States or India, but is a leading cause of sudden cardiac death in athletes.  So it’s reasonable that I may not have heard of HCM in my family, because it may never have been diagnosed.  But I called my mother anyway and started asking questions: do we have any heart disease in our family?

I was surprised to learn that the answer was an emphatic: yes.  Though we had never discussed it, my mother was similarly surprised that I didn’t know that the majority of deaths in my family were related to heart disease.  My grandmother, who I thought had died of diabetes, actually suffered from angina and died of heart failure.  My grandfather on my father’s side had early-onset heart attacks and died from a blood clot.  Their brothers and sisters?  Cardiac arrest.  I even had a middle-aged cousin I never met who died the month before due to sudden cardiac death.  And all this time, at the doctor’s office, I never checked any box related to heart disease in my family history.  This information wasn’t recorded, anywhere, except the notepad I was using.

Given the surprising prevalence of heart issues on both sides of my family, it was hard to pin down which of my parents was likely to carry my mutation, so I got them both genotyped by 23andMe.  From there, it was easy to determine that the mutation came from my father’s side, which had more of the early-onset heart attacks.  I explained the research paper and its caveats to him and told him to talk to his doctor, then hung up the phone and realized: “Wait, shouldn’t I talk to my doctor?”

How do I even bring it up?  I’m a member of an HMO (Kaiser), and I like my primary care physician.  He’s always taken me seriously and referred me to the appropriate specialists, but he’s not a geneticist and I’m sure he’s never heard of this mutation, this gene, or this paper.  I was afraid he would laugh at me if I tried to explain that I bought a test online and found a mutation that suggests I should be screened for HCM.  But that’s what I did, in a nutshell, and to my surprise, he called up cardiology right away.

The cardiologist had never heard of this mutation, either, and went so far as to claim that there aren’t any such dominant mutations in MYBPC3.  All right, the paper came out in 2009 and, living in North America, I didn’t expect a South Asian variant to be well-known, but I didn’t expect the cardiologist to speak so authoritatively on something he was clearly wrong about.  My physician, to his credit, referred me to the genetics department and sent me home.

The geneticist who called me back was surprisingly informed and began the conversation by apologizing for the misinformation the cardiologist gave me.  She was particularly disappointed because she had recently given a talk about mutations in MYBPC3 to that department.  She also hadn’t heard of this mutation, but asked me to forward her the relevant papers and spent a week reading them.  She said that this would be considered a “variant of unknown significance,” but because of the deletion being in MYBPC3, I should be screened for HCM anyway.

I was referred back to cardiology for testing.  I took a resting and stress test EKG that indicated a worrying drop in blood pressure after exercise and an unusually long recovery time (consistent with my experiences attempting to work out).  I got an echocardiogram which didn’t detect HCM but found abnormal wall motion in my heart.  I spoke to another cardiologist who told me: “you aren’t 40 yet, so you aren’t at risk.”  The results were forwarded back to my physician, who summarized them as “normal” and sent me home.

I’m a scientist and I’ve worked professionally with clinicians in the past.  I know how the population statistics work and why they sent me home.  It doesn’t make economic sense for an HMO to spend any more money on me, when they can’t treat the condition, anyway.  But as an individual, this was unsatisfying.  What could I do to empower myself?

A lot of things.  I started dieting and losing weight.  I increased my activity level with more standing and walking, did more yard work and less video gaming.  I cut out a number of stressful activities in my life.  Today, I’m still South Asian, I still have this mutation, and I’m not getting any younger. But I’m back to a healthy BMI. I have an active lifestyle, I e-mail my doctor regularly to keep in touch, and I have a well-documented family history of heart disease.  Most importantly, I’ll be regularly screened for HCM from here on out and that’s one disease that won’t catch me by surprise.

Results not typical. Results vary due to unique differences in each individual’s DNA. On average, users receive at least one or two results that may help with proactively managing health.  23andMe’s services are not a substitute for professional medical or diagnostic advice.


  • Ra

    interesting. glad you are proactive about it. This is the power of identifying mutations…

  • http://www.facebook.com/johnlloydscharf John Lloyd Scharf

    It sounds like you are powerless to use your information for diagnosis and treatment.
    There are meds to avoid and treatments available:
    http://en.wikipedia.org/wiki/Hypertrophic_cardiomyopathy#Treatment

    I have had similar experiences with physicians.

  • Brian Vroomen

    Inspirational! I think this story is a good nutshell version of what we all should be aware of when it comes to knowing the results of our genetic testing. Don’t think that the doctor really does know best. They will sound authoritative, but that does not mean they actually are an authority to be listened to. I love my doctor. He does listen to me and we can converse as peers. Thank you for sharing your story.

  • Ryan Morville

    Nicely done. It’s so important for individuals to take initiative in investigating their own health maladies, potential or immediate. Way to rely on gut instinct!

  • ct

    I’ve found it amusing that
    1. a worrying drop in blood pressure after exercise
    2. an unusually long recovery time
    3. an abnormal wall motion in the heart

    is interpreted as
    a. you aren’t 40 yet so you aren’t at risk
    b. your physician summarized the results as normal

    also
    A. I’ll be regularly screened for HCM from here on out
    B. That’s one disease that won’t catch me by surprise

    You do realize that sudden cardiac death is the usual clinical presentation leading to the diagnosis of HCM?

  • Arnab Chowdry

    @ct:
    To answer your question, sudden cardiac death leads to the diagnosis of HCM for the reason I mentioned in the blog post: nobody gets screened for HCM ahead of time. If I develop HCM, regular screening will catch it (hopefully) before I suffer sudden cardiac death and that will help me to avoid activities that might increase my chances of death (eg. running a marathon!). If I didn’t have this clue to my chances of developing HCM, I would never have been regularly screened and it really would have been a surprise.

  • Atul Kapadia

    I have a similar experience with age-related macular degeneration. I am a South Asian (from India) and thanks to 23andme started preventive measures against this disease. There is no cure but the risk can be reduced by a bunch of different measures.

    Thanks 23andme.

  • http://www.gapup.com Benjamin

    Hi Arnab,

    I read your story and if you’re in the Bay area I strongly encourage you to to speak to someone at the Hypertrophic Cardiomyopathy Center at Stanford. You might also wish to get in touch with the Hypertrophic Cardiomyopathy Association (4hcm.org).

    There is a shocking difference in the knowledge and advice given by ‘general’ cardiologists vs. those who specialize in HCM. Unfortunately, all too often this is a life vs. death difference.

    Best of luck to you.

  • Ramesh Hariharan

    I have one copy of the 25-bp deletion in MYBPC3 (probably the same mutation you refer to above). I am South Asian (South Indian, to be more precise). My father has been hypertensive from a young age but other than that there isn’t an unusual history of heart disease in the family (of course, I don’t have too many data points to go by). I have been physically active for a long time, I run 5K at least 4 times a week, swim on the other days, bicycle to work, and run the occasional 42K marathon. So far I haven’t felt the slightest symptom, which of course doesn’t say much, given that HCM is known to cause sudden deaths; further, as the 2009 paper shows, symptoms are likely to appear between 45 and 60, and I am still a couple of years shy of that bracket. So indeed worth watching out. I guess I need to figure out how to get screened periodically here in Bangalore.

  • Alistair Sammy

    Arnab I just found out that I also have the same mutation as you, I will also make changes in my lifestyle. My mother had her first heart attack at 47, open heart at 48 and she’s now 60 with heart problems, her mother passed away at 54 from heart disease, and all of my mother’s Maternal uncles passed away in their 40′s and 50′s with heart disease. I’m of South Asian origin as well, and this made me realize how I needed to make changes ASAP. I realized a long time ago denial is not my friend. Glad to talk to someone about this. I’m in my mid to late 30′s, and I’m looking forward in a long and healthy life God willing.

  • Steve Thomas

    I have HCM. Perhaps you have this (genetic) disease. In my opinion, there are only a few cardiologists how can understand and help. One of these is Nishimura at Mayo, MN. In my opinion, with this gives me perhaps more 30 years of good life (I am 65), as opposed to my younger brother who died from HCM age 52. Go check you heart at Mayo, Cleveland Clinic (Ohio), Johns Hopkins Hospital, in my opinion no where else. In my opinion, HCM comes from a “muscle-cell-tangle” (sarcomeres, myocardial disarray) in left ventricle of the heart, sets up a murmur, growth of the cardia septum, palpitations, and a heart very big and bad efficiency, all over time. Catheterization (of the heart) is my opinion is the best lab test to determine if HCM is there, even for young people.

  • Mary

    Wow Arnab. I had no idea that HCM could be caused and carried through a family by a mutated gene. I recently had the pleasure of working with Darla Varrenti and Jonathan Drezner on the subject of sudden cardiac arrest in, specifically, young athletes. Not really the area you talk about – but as you noted, it is the number one cause of death in young athletes. These two people, together with the University of Washington Medical center, put together a podcast episode on how HCM is not well known and how having a heart screening as a regular part of a sports physical can make a massive impact in preventing related deaths. Here’s the link: http://www.uwmedicinepulse.com/saving-lives-in-the-nick-of-time/.

    There’s still so much we don’t know about heart conditions, it’s awesome to see someone like you being so proactive in figuring it out for yourself, your family, and through that, others.

    Mary

  • Theresia Wikström

    I also have the same mutation and i’m Swedish and so is my family for many hundred years as we know it.

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