Tag Archives: whole exome sequencing

Two NUBPL Families Meet For First Time, 2,000 miles apart

A little over two years ago, we received Katherine’s results for Whole Exome Sequencing (WES), giving us a name, NUBPL, to the disease that was a mystery to her doctors and is responsible for the atrophy of her cerebellum. Although we finally knew the name of the mutated gene, and that it was considered a rare form of Mitochondrial Complex 1 Deficiency, we didn’t know much more than that. In fact, at the time we quickly learned that her disease was recently discovered.

Although we were elated to receive a diagnosis, we realized that we didn’t know how the disease would affect Katherine’s life. Her doctor had never seen another patient with NUBPL, so he didn’t have much to tell us in terms of disease progression.

We searched the Internet looking for any information we could find, which included a couple of scientific articles citing six patients from 5 unrelated families. From these articles, we learned more about the patients, including sex, age, country of origin, clinical signs, MRI details, when and if they walked independently, and cognitive function. We had no way of contacting any of these families without knowing their names or doctors. We didn’t even have a photograph.

I felt like a detective scouring the Internet hoping to find a clue. I started tagging everything we shared with “NUBPL” and searched the Internet several times a day for a signal from anyone out there who had this disease. I posted in Facebook groups and wrote blog posts, anything I could think of that might put us in contact with another family with this same disease.

Just a few weeks later, I was looking through posts on the Global Genes Facebook page when I noticed a post from a mom sharing a link to a documentary about their 14-year journey to a diagnosis for both her daughters who were diagnosed with NUBPL. As I watched the documentary, tears rolled down my face as I picked up the phone to call Dave to tell him I’d found another family. And that they looked happy and one was walking independently. After living with a misdiagnosis for nearly two years of a quickly fatal disease, I’ll never forget the moment that I saw the smiling face of a 16-year old girl with same disease as Katherine.

Everything is about perspective in this life. After being told that my child was going to die by the age of seven, that first glimpse at Cali Spooner’s face added  years to my child’s life. In her photograph I saw Katherine smiling back at the camera. For the first time, I saw Katherine as a teenager.

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And then I saw Ryaan Spooner’s face and recognized my Katherine in her as well. And she could walk independently. Their body types were even similar.

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The Spooner Family

I got off the phone with Dave and contacted their mom, Cristy, who responded immediately and we’ve been in contact ever since. She put us in touch with their doctor at UC-Irvine, Dr. Virginia Kimonis, who was growing fibroblasts to learn more about the disease. We contacted Dr. Kimonis and sent Katherine’s skin biopsy for research.

Last week, our family traveled to California to attend the first NUBPL Family Conference at UC-Irvine and to spend time with the Spooner Family.

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We heard from several researchers and toured the lab where they have been growing our daughter’s fibroblasts.

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And a few days later, we were able to introduce our girls to one another for the very first time.

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Both of our families instantly hit it off as we watched our girls play together. We were all sad that the night had to end and we had to go back to living on opposite coasts.

Katherine and Ryaan share a love of dolls and both are fiercely determined and independent. They are very similar in many ways. Katherine watched Ryaan walk independently, which she learned to do at Katherine’s age (they are two years apart). After seeing Ryaan walking, Katherine is now determined more than ever that she’s going to do the same. And I know she will.

Our girls are three of 11 NUBPL patients identified in the world. After spending time with The Spooner Family, I am reassured more than ever that we will find more NUBPL families in the future. These things take time and we are just getting started.

We are two families brought together through science, hope, love, and a fierce determination to give our girls the best chance possible at life. Where science hasn’t caught up, we will fund the research ourselves through our non-profits. Where there are barriers to diagnosing more patients in the future, we will spend our time to eliminate those barriers. And when we cannot find those patients as they are diagnosed, we will do everything we can to make sure they can find us.

As our families were spending time together in California, a mom with two daughters made contact with both of us. Yes, I am hopeful that we will grow our NUBPL community.

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NUBPL Gene – Mito Complex 1 (Diagnosed)

February 2015 – Katherine Belle was DIAGNOSED through Whole Exome Sequencing: Mitochondrial Complex 1 – NUBPL Gene.

We want to introduce you to the Spooner Family and their daughters Cali and Ryann, both of whom have mutated NUBPL genes like Katherine. We were undiagnosed for only two years…their oldest daughter was undiagnosed for thirteen years.

Although not identical, I can tell you that after seeing this video I immediately saw similarities between our daughters. After being misdiagnosed for so long with something that didn’t feel right in our hearts, it is so comforting to know and accept the correct diagnosis.

Please watch this video when you get some time. It’s lengthy, but very important and inspiring: The Life We Live

We are all interested in finding others with the same diagnosis.  They may contact me at gcmccoy1@aol.com.

Connected To The Past

Timing is everything in life.  Just as those who came before us, we all have a ticking clock over our head.

Lately, I’ve frequented antique shops scouting out props to use for food photography projects and collaborations.  More than ever I feel a greater connection to the past.  I find it impossible not to think about the lives, conversations, relationships, tragedies, etc. of the previous owners as I touch, repurpose, and use their personal household items.

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My most recent excursion brought tears to my eyes when I stumbled across a beautiful wooden cradle sitting silently in the corner. That cradle belonged to somebody else’s Katherine, and the bond between a parent and child is timeless.  What was that baby’s story?  Did she have a long, healthy life, or did she die young from Scarlett fever, influenza, an appendicitis, or a rare disease?

Although many medical advancements have occurred since that cradle was made, it’s hard not to feel stuck in the past when doctors say they believe your child is slowly dying of a disease they cannot diagnosis or treat.  Intellectually, I grasp and appreciate the fast-paced nature of genomic medicine; emotionally, however, I fear my own daughter’s timing may not be on the right side of science.  Then again, children still die from influenza.

None of us can escape death or its timing.

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Silhouette of Katherine Belle by Clay Rice.

As I closed my eyes and filled my mind with the sound of giggles and the tender moments shared between a mother and her child, I was reminded that hope is the only thing stronger than fear.  Yes, I am afraid, but my hope and faith are much stronger than my fears.

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Now What?

Now what?  That’s the million dollar question.

We find ourselves in that place where nobody wants to live.  A place somewhere between a 90% diagnosis of something horrible and untreatable and an unlikely diagnosis that your child has that disease.  No doctor calls to check on your child; no medicine is given; no advice is offered.  All you know is that your child’s condition is worsening, yet the medical world is silent.  You’re sent back home with nothing actionable except for the things you can research on your own.

There isn’t a single word I know that can adequately describe this place.

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At least everybody can agree on a few things: 1) Katherine’s MRI shows that whatever she has is spreading throughout her cerebellum; and 2) whole-exome sequencing is the next step and might lead us to answers.

Just one minute after reading Seth Mnookin’s New Yorker article, “One of a Kind” about the intersection of social media, genomics and rare diseases, I contacted Matt and Cristina Might.  It was not until that very moment that I realized (and truly digested) the crucial role we, as parents, play in diagnosing our daughter’s rare disease.  The Mights have been very helpful and introduced me to other families on a similar journey.  We hope to meet up with them sometime in the future, perhaps at the upcoming Global Genes Rare Patient Advocacy Summit in Huntington Beach, California (we are still in the process of deciding whether or not we can attend)?

In short, I have updated my current job status to “rare disease hunter,” which involves taking on Congress and encouraging each member to join the Rare Disease Caucus.  Just today I received a message that Representative Andy Barr (KY-06) is joining the caucus after reading our blog and letter I sent him.  Hooray!  Congressman John Yarmuth (KY-03) is also a member of the caucus.  Anyone want to help get the rest of the delegation on the Rare Disease Caucus? It only takes three minutes of your time to submit a request. If they are already on the caucus then your message will be sent as a “thank you!”  Simple.

Click here to ask your Representative to join the Rare Disease Caucus. (Mention Hope for Katherine Belle.  Send them to our blog at http://www.hopeforkatherinebelle.com.  Put a face to rare disease.  Tell them rare disease is a non-partisan issue.  Tell them it matters to you.)

In the meantime, in addition to contacting all family members and collecting every piece of genetic information available while reading “Genetics for Dummies,” I have decided to take a new approach to treating Katherine’s “unknown/untreatable” disease:

1.  Next Tuesday we have an appointment with a local Integrative Medical Expert who can evaluate her body as a “whole” and address nutritional and supplemental concerns, including the brain inflammation we are seeing on her MRI;

2.  Beginning last week Katherine had her first cranial-sacral therapy session, which she throughly enjoyed and said, “no shot” when it was over.  (I also noticed she was less shaky following this session!) For those of you who are not familiar with cranial-sacral therapy, it is “a form of bodywork focused on the concept of ‘primary respiration’ and regulating the flow of cerebrospinal fluid by using therapeutic touch to manipulate the synarthrodial joints of the cranium;

3.  We are very seriously researching the possibility of hyperbaric oxygen therapy; and

4.  We plan to take her to an immunologist at Duke.

Moving into fall, on October 6, 2014, we are taking part in our first whole-exome sequencing (WES) study at UNC – Chapel Hill. We also hope to do another WES test through Baylor once our insurance company tells us how much they will cover (crickets have been chirping since the end of June).

Results for these tests can take up to seven or eight months.

We continue to do physical and occupational therapy once a week.  I would also like to find the time to add some music therapy into our routine.  And, yesterday we signed the papers to put our house on the market…finally!

How Social Media Impacts Scientific Research

This article in the New Yorker is by far the most important article we’ve read to date that defines our purpose and hope for Katherine Belle.  Thanks to the Mights and Wilseys for confirming what we hope to achieve and proving there are other options than just waiting and hoping science “catches up.”  When parents are given no other option but to create websites and post articles with their genetic data to accelerate research and treatments for our dying children, there is a serious problem with the system.   We are an important part of the diagnostic team and can play a critical role in helping decipher the human genome.  My question is why aren’t more journalists talking about this problem?

Matt Might gave a talk titled “Accelerating Rare Disease.” After describing the effects of his blog post, he told the crowd that it was inevitable that parents of children with other newly discovered diseases would form proactive communities, much as he, Cristina, and the Wilseys had done. Vandana Shashi believes that such communities represent a new paradigm for conducting medical research. “It’s kind of a shift in the scientific world that we have to recognize—that, in this day of social media, dedicated, educated, and well-informed families have the ability to make a huge impact,” she told me. “Gone are the days when we could just say, ‘We’re a cloistered community of researchers, and we alone know how to do this.’

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Around We Go

On June 19, 2014, we were told a second time by a doctor that, in his opinion, he thinks there’s a 90% chance Katherine has Infantile Neuroaxonal Dystrophy (INAD). Once again, this opinion is based solely on her brain MRI.  However, (at this point) she shows no clinical signs (i.e. involuntary eye and muscle movement, muscle rigidity, etc.) of INAD.  We are still awaiting some results from her spinal tap. All other tests, including those that typically show abnormalities in INAD patients, have been normal except for her brain MRI.

Feeling confused by the certainty of the diagnosis based on the MRI alone, we decided to seek a third opinion, this time from an INAD expert in Oregon.  We sent her all of Katherine’s test results, MRI reports and images, medical history, etc. After a thorough review, she informed us that she thinks it is unlikely that Katherine has INAD.

Again, an expert in the family of diseases that include INAD says she thinks it is unlikely that Katherine has INAD.  Unlikely.  Unlikely is a far cry from a 90% likelihood.

Without getting too technical, Dr. Hayflick says the progression shown on Katherine’s last MRI is not the same as she’s seen in other INAD patients, and one abnormality is not one she has ever seen in an INAD patient. In addition (as we knew), the genetic test results for INAD were normal.  She also believes she should be experiencing clinical aspects of this disorder other than those directly associated with the cerebellar atrophy, which she is not.

So, where do this leave us?  Is this a cause for celebration? Well, we do not know what this means since she did not give us any alternatives.  Instead, she agreed that the next step should be the Whole Exome Sequencing for possible answers.  We are in the process of getting the test cleared through our insurance company (fingers crossed).  This test costs around $13,000.  Insurance may or may not cover some or all of the costs.  Test results take four months.

It is likely that this test is the end of the road for us as far as conventional medicine is concerned.  Few of the things Exome Sequencing might reveal have FDA-approved treatments – but “few” is better than “none.” Four months from now we may be left with this answer: we just don’t know right now.  Or, this test could uncover something other tests have missed – perhaps a disorder that is treatable. Perhaps it will reveal an atypical INAD, leaving us where we were last August and again last month.

For now, we must be patient, enjoy our precious moments with Katherine, and have faith in the things we do not understand. This journey continues to confirm my belief that Katherine truly is rare –  a living, breathing miracle who is spreading her joy around the world – and none of her doctors have ever seen another person with her condition.  We all seek answers under these circumstances, but for now they can only estimate with percentages as to what is happening in her body because they are not certain.   And, as uncomfortable as it may feel at times, uncertainty isn’t necessarily a bad thing.

After all, hope shines brightest in the darkest moments, right?

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