PURA and Simple

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PURA and simple….except that it’s not.

This new finding, this PURA gene gone wrong, it’s anything but simple.

Thirteen years without a diagnosis and now we have one. That’s a lot to take in.

It feels less like closure and more like a new beginning.

And speaking of beginning, this new diagnosis has taken me back to Aidan’s early days. I had so many questions and no one really had answers. I was mostly overwhelmed, scared and grieving. Those emotions are remembered deep in my bones and have been quick to surface and pull me down.

Now Aidan has a diagnosis, unofficially. This comes with a new set of questions, a whole new language – truncated genes, alleles, transcription – and still few answers.

I’ve met five other moms who have children with the same genetic variants as Aidan. These are the people I longed for in my early days when my son was born before Google. We’ve been discussing our children’s similarities, sharing scientific journals, asking each other questions. It’s exactly what community should be.

I want to invite them over for beer and nachos and a long weekend of talking and laughing and most likely crying too. I want to meet their children and see if I can detect that shared message tucked away in their 5th chromosomes. Of course we’re spread out all over the globe and they may be super classy so perhaps we should have wine and chocolate and borrow some fancy table clothes. But they’ve survived traumatic medical events too, so beer and nachos and wine and chocolate it is.

There are moms with young children in our group and I am reminded why we did genetic testing in the first place; it became less about Aidan and more about the future and potentially helpful scientific discoveries. I suppose I knew they were there all along.

I’ve felt very torn about my story. On the one hand, I want to hug these moms and say, “There is so much hope and you will find depths of yourself that you didn’t know existed. You will need  that strength to survive hard things and you will. You will survive and thrive. Your child will be ok. Not walking and talking is not the same thing as not having any power to explore the world and discover and have fun and learn and communicate and love.” On the other hand, I’m not entirely sure that would have sounded like hope to me in the early days. I think I’ve become exactly the person I needed that I didn’t really want to know. Hope should feel bigger and yet it still takes up all the space inside me.

I found my sherpa too, my been there done that mom who will stand with me. She’s raising a teenager with a rare genetic diagnosis, popped out a baby then rocked a black dress at a foundation function, participated in a genomics conference using big fancy science words, then swore just the right amount about her entire journey to me on the phone. She’s holding hope for me in my heavy new beginning.

I went on a date with my husband last week. Our dates are rarely what they should be. We crave lightness and intimacy and romance on demand, which can seldom be delivered. I failed in parenting the night before. My precious Liam sat down next to me and asked me about my day. I was too caught up in the frenzy of the need for us PURA moms to do something and the overwhelming science of what I’m trying to understand. I ignored him. I carried all of that failure with me on our date and cried over my pasta. Garreth doesn’t quite feel the weight of this new journey, the strain of the questions and the burden of responsibility. I cried a little more, asking him why genes are so complicated and wondering when the waiter would be brave enough to bring our drinks over. As is often the case, the tears led to laughter.

None of this is simple. I’m excited to be on the cutting edge of science and I’m grateful that I’ve found other moms on the same journey.

I’m also remembering trauma, holding hope, and trying to make sense of it all.

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The Stop Sign in Aidan’s Genes (PURA GENE)

I have something special to show you, a little piece of yourself.

But first let me tell you why it’s so incredible to me.

My son Aidan was born 13 years ago with an undiagnosed developmental disability so for 13 years I’ve been watching human development in slow motion. The strength of our muscles, the authority of the brain, the power of the body to heal. The same brain that’s made it difficult for him to walk and impossible for him to speak, has also given him the cognitive ability and dexterity to drive a power wheelchair and find other ways to communicate.

For 13 years Aidan’s medical team has been searching for a cause of his medical issues. For 13 years we’ve come up empty handed.

Until now.

Six months ago Aidan’s whole exome was sequenced and we found two genetic mutations.

Allow me to show you your PURA gene:

MADRDSGSEQGGAALGSGGSLGHPGSGSGSGGGGGGGGGGGGSGGGGGGAPGGLQHETQELAS KRVDIQNKRFYLDVKQNAKGRFLKIAEVGAGGNKSRLTLSMSVAVEFRDYLGDFIEHYAQLGPSQPPDLA QAQDEPRRALKSEFLVRENRKYYMDLKENQRGRFLRIRQTVNRGPGLGSTQGQTIALPAQGLIEFRDALAK LIDDYGVEEEPAELPEGTSLTVDNKRFFFDVGSNKYGVFMRVSEVKPTYRNSITVPYKVWAKFGHTFCKYSEEM KKIQEKQREKRAACEQLHQQQQQQQEETAAATLLLQGEEEGEED

Each of those letters represents one of the 322 amino acids on your PURA gene. You had no idea how complex and amazing you are, did you? This is a very specific code of instructions. I can’t comment much on the science partially because it’s all still confusing to me and also because the PURA gene has not been studied enough in humans.

Now let me show you Aidan’s PURA gene:

MADRDSGSEQGGAALGSGGSLGHPGSGSGSGGGGGGGGGGGGSGGGGGGAPGGLQHETQELAS KRVDIQNKRFYLDVKQNAKGRFLKIAEVGAGGNKSRLTLSMSVAVEFRDYLGDFIEHYAQLGPSQPPDLA QAQDEPRRALKSEFLVRENRKYYMDLKENQRGRFLRIRQTVNRGPGLGSTQGQTIALPAQGLIEFRDALAK LIDDYGVEEEPAELPEGTSLTVDSKRFFFDVGSNKYGVFMRVSEVKPTYRNSITVPYKVWAX

Where you have an N Aidan has an S. These both have similar functions and so this variation may or may not be a problem. However, where you have a K, Aidan has an X. Look what happens after the X. Nothing. X is a genetic stop sign. Aidan has incomplete instructions and that is definitely a problem.

These are de novo mutations in Aidan, more specifically, he did not inherit them from his dad or me. Many of us have changes in our genes that are of no particular consequence.  But sometimes it’s life altering.

As genetic testing becomes more affordable and readily available, we will be learning more about previously undiagnosed children. This conversation is going to become more commonplace. We will all need to work together to understand what we learn. While there is enough information about the PURA gene to believe that it’s causative in nature to Aidan’s medical issues, there is not enough information to give Aidan an actual diagnosis.

There is work to be done. Research. Studies. People looking into microscopes, gathering information, and writing long, in depth papers.

This is why their works matters to me:

Aidan Back Surgery 0298

Photo: Rick Allen

I am 13 years into this journey and no longer in trauma mode. I have the endurance to fight Aidan’s medical battles and the privilege of celebrating his achievements.

But there is some mom in a NICU somewhere whose child has a genetic variance that could be causing problems. This is my moment to help her, my chance to reach back in time a little and remind myself that I’ve never really been alone.

I hope that you will join me.

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Here’s how you can help:

1. Share this post. If you doubt the power of social media, read the article, “Hunting Down My Son’s Killer” which brought families and researchers together and eventually led to the formation of the Grace Wilsey Foundation which is committed to fighting this particular disease. Their journey is chronicalled in this New Yorker article. So please, share.

2. If your child has a genetic mutation on his/her PURA gene, I would very much love to hear from you.  teamaidanrocks@aol.com

3. If you’re a scientist who would like to suggest reading for me or any other information, I would greatly appreciate that as well.

For another great read from a parent with a stronger science background, check out Dana’s post here.

Take all of the scientific information with a grain of salt as I’ll take metaphors and colorful words over codes and patterns any day. And thank-you to the REAL Dr. Bowie for ongoing   help. (Yes, longtime readers, their are two real Dr. Bowies in the family and neither one of them is me.)

Genetics Update

Last week Garreth and I sat down for a science class with Aidan’s fabulous geneticist. She’s been following Aidan’s progress since birth and has already tested him for many genetic anomalies. A specific lab is offering full exome sequencing at no cost to us. This will be the most complete look at Aidan we can get right now and may give us some insight into his specific medical issues.

I’m going to refrain from giving you the full on science of what we learned because I’d probable screw it up because our bodies are so amazingly complex and this test is so very detailed and the field of genetics is constantly changing.

Here are the basics; please take this with a grain of salt.

The exomes are the protein coding part of your genes, and though the exome is just a small portion of the entire genome, the exomes are responsible for most disease causing mutations.

First the lab will look at Aidan’s exomes. They will look for suspicious deletions, duplications, or sequencing issues. They will sequence specific exomes that are known to cause medical issues related to Aidan’s neurological and developmental issues. They will also look at exomes that could reasonably be expected to cause disease.

They will find variations, possibly thousands of them. We all have mutations that actually have no impact on our health. They need to figure out if any of these exomes, or perhaps combination of exome mutations could be causative in nature for Aidan. It’ll be an interesting hunt.

They will compare Aidan’s exomes to a control group and, or course, to us, his parents. They will find extra genetic material on his third chromosome and then they will find it on mine because it’s shown up in previous genetic testing. Because it has caused no medical problems in my body, it’s not the source of medical problems in his. They will look for something that shows up specifically in Aidan that doesn’t show up in us, or possibly a strange combination of mutations that he received from Garreth and I that possibly caused a perfect storm.

Here’s where it gets sticky. We signed a consent form that gave them permission to look specifically at genes that are known to cause certain diseases that can be prevented or treated. (Think Angelina Jolie and the BRCA breast cancer gene.) These genes won’t give an answer to Aidan’s diagnosis but may give us useful information regarding Aidan’s general health. For example, there is a gene mutation that will only effect you under anesthesia. That’s very specific and rare but it could be deadly when it’s very preventable. Aidan most likely doesn’t have this because he’s successfully been under anesthesia several times, but he will have more surgeries in his lifetime and this is helpful information. Because Aidan is non-verbal and can’t give us specific indications of pain or illness, we want whatever information we can get about his health risks.

If he is found to have any of these disease causing genes, they would look at our blood samples to determine if Garreth or I have them as well. Garreth and I do not walk away with a clean bill of health because they are only looking at our sequences as they relate to Aidan. I will not be certain if I carry the BRCA gene, for example, unless Aidan does because they will not look specifically at Garreth and me without cause.

It’s all very fascinating. Aidan may or may not come away with a diagnosis. He could have a very rare combination of gene mutations that little is known about. He could have a very specific mutation that has no treatment indications. I’m ok with all of that. Twelve years later I’m in a very different place then when Aidan was born. I know we’re not alone in being undiagnosed; I know that he will continue to make progress; I’m more comfortable with his required level of care. It’s been an emotional roller coaster and I can’t quite anticipate where I’ll be with all of this in another decade.

For now, I hope this science helps the next baby who lands in the NICU without a diagnosis.

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Any questions?