Genetic Findings: TUBa1a, transitions, and proteins, oh my!

Genetic Findings: TUBa1a, transitions, and proteins, oh my!

I received a phone call with regard to our genetic testing. If you’ve been following since “the beginning”, you may recall we have previously tested chromosome 17, and DCX gene, both of which are commonly found to be tied to Lissencephaly, but those results came back clean. We tapped the breaks on what could have been an expensive chase, and decided to focus on different things for a while.  I brought the topic back up after their 2nd birthday, so we ran whole exome sequencing through GenDx this time, with the support of our Chidren’s hospital.  And at no cost to us!

L was the “patient”, although J, N, and myself were tested as well. What was found was a NEW mutation. Neither J nor I were genetic carriers. It was not a chromosome disorder but in terms of location, was on 12q. More specifically it was the TUBA1A gene. TUBA1A is important in brain development. Mutations within it are not currently known to cause other body or organ issues, (not consistently linked to renal disease, deformations, etc) When this occurs, it is Autosomal Dominant. So in other words it is NOT present in big brother K in a recessive form.

Within TUBA1A, their specific mutation was on 652 – G to A: In the DNA sequence, there is a misspelling on a base pair. They have an A (adenine) where they should have a G (guanine). This type of mutation is referred to as a transition. It caused a change in the protein D218N. All of the above leads to a neuronal migration disorder as cells are aligning during pregnancy.

Their specific mutation had been as of yet unreported, but because nearby similar mutations have been reported on TUBA1A and known to cause Liss, they are confident this is the genetic issue.

According to the genetic counseor, TUBA1A mutations are found in only 1% of Classic Lissencephaly. (And Lissencephaly is already a rare 1 in 100,000)

They are not sure what causes this new mutation, but it is believed to be random with no known predisposition. That means the chances of recurrance are “very low”. They assign it less than 1%. I know of other families who were told something similar with other findings, yet had a reoccurance with a later child. When I asked if that means that possibly the combination of our DNA can be more likely to cause this mutation, she said no. But it is possible that even though the results are not in our blood, there could be mutations on a particular egg or sperm.  (I believe this is called being a mosaic carrier but I have more to learn about this part).  So while the existance of other mutations is unlikely, and the chances of getting pregnant with one of those if it does exist is very rare, they can never say 0% with confidence.

We were willing to hear if they discovered any other genetic predispositions (cancer, Huntington’s, heart disease, etc). There were no such secondary findings on L so therefore no further searching for those in the rest of us.

What does all this mean?  Beats me.  I wish I had paid more attention in biology back when they were talking about base pairs.  But I’m eager to see what I can round up to understand this better.  If you understand this sort of thing, feel free to chime in, or help me with intelligent questions.

What does all of this mean for L and N?  I can find families who are dealing with a much more specific, and seemingly similar set of circumstances.  Fellow moms have been a tremendous resource so far, and now I can hone in on a group who fits “us” even more and hopefully also offer similar support and ideas.

As far as their prognosis or severity changing…it doesn’t.  They’ve always been L and N, I’m just on a path to understanding them a bit better.  But they were precious and loved yesterday and they are precious and loved today.

2016 Denim Dash – We have a team!

I am proud to announce we have a team for the 2016 Denim Dash, raising funds and awareness for rare disease research. You can click this link if you are interested in donating, or joining in our virtual run on March 19th. I will continue to post updates, facts, and stories leading up to the race date. I am posting today because there is early bird pricing available to runners who sign up by January 28th.

Today’s fun fact – we were among the top fund raisers last year for the first ever virtual denim dash, and the most active on social media. If you visit the page, you will see a lot of familiar faces in the background from last year’s participants.

Thank you for caring about rare!


Free yogurt

Free yogurt

It has been a strange day.  I try to live day to day in this life with the boys, knowing anything is possible, and to prepare my mind as such.  If you know anything can happen it is harder to be caught off guard or let down.  Today I woke up thinking I KNEW we were going home.  It was a rookie mistake, and unfortunately I wasted a day in a time when all days are precious.

What I haven’t told you is that L passed his first room air trial Friday night.  In fact, we were almost discharged Saturday, but as he sat there on room air Saturday morning, the Dr asked my comfort level and how things were looking. I said I wasn’t opposed to observing him another day to be sure it would “stick”, because L has a way of hiding his distress.  I kid you not, DURING that conversation, his stats dropped again and he couldn’t rebound without help.  As luck would have it, the Dr observed, my concerns were confirmed, and we agreed to give him another day and reconvene on Sunday.

As Sunday came and and went, we saw more of the same.  Stints on room air, bursts where he needed oxygen.  He was more alert, looking around, but still needed help.  Maybe he just needs oxygen until he fully recovers?  Maybe he needs it all the time now?  We can go home on oxygen with his current level of health.  Let’s observe another day and involve pulmonology and home medical equipment on Monday.

Monday I woke up confident.  Everyone else seemed to too.  Case management was on top of things, oxygen was delivered to the house, and a rep drove all the way to the hospital to deliver our travel tank.   We started talking about an exit x-ray, and follow up appointments.  I spent half the afternoon standing around with my virtual coat on and keys in my hands.  I even loaded our things in the car.  (PRO TIP – NEVER DO THAT UNTIL YOU HAVE DISCHARGE PAPERS!)  The x-ray returned, and that combined with my discussion with pulmonology spurred further disussion.  It looked the same.  If it was aspiration pneumonia, why wasn’t it worsening without antibiotics, and why weren’t we seeing signs in his bloodwork? (Those aren’t a must, but they are part of his history).  If it was viral pneumonia, why was it still there, just as strong as the last few days, while he seemed to be back to baseline.  And a question we’ve been asking of anyone who will listen…what about his cold temp, and dipping heart rate?  Are they related to the perhaps not so acute respiratory distress?  What are we missing?  A theory (re)emerged.  One that our home nurse has pondered as well.  Maybe all of these things are connected.  Maybe there is no virus, no aspiration, and instead, maybe L has been having cardiac distress, leading to pulmonary edema.  If his heart isn’t pumping efficiently, it can lead to fluid buildup.  And that can present as a respiratory issue.  The only way to confirm is to do an echo, and get cardiology involved.  So we’ll learn more on Tuesday.

Adding a potentially chronic problem weighed hard on me at first.  Not that an acute illness or  event is any “safer”.  Either can become life or death when it comes to L.  Honestly, I just didn’t wake up today “ready” for anything except good news.  I had decided what I wanted, what I needed, and wasn’t prepared for anything else.  That presents as optimism, but it plays out as entitlement.  And I know better.

There are meds to fix this, and the fact that we had the forethought and awareness to test , rather than send us home prematurely may be a life saving catch for L.  We could also be wrong, and the x-ray may just be trailing behind his recovery.  But we will know more soon.  And now that the dust has settled, I’m feeling grateful for the opportunity to check.

This is me getting my stuff back out of the car.  This is perhaps the hospital version of the “walk of shame”. 



This is L, telling me to get over the pity party and distracted day, and get back to cuddling.


So I did.  I set back up in the room.  I decided to get some exercise since I had spent the day hovering instead of moving.  So I went and jogged the hospital stairs (inside) for a few minutes. I grabbed a quick dinner.  Maybe it was the lingering glaze on my still puffy eyes, from the pity party.  Maybe it was the flat out sweaty appearance and wild hair I had from my attempt at a cardio routine.  But “Jimmy” from the cafe said “your frozen yogurt is on me tonight”.

Long story short, I’m not packing my bags early tomorrow.  I’m not waking up thinking I know where the day is headed.   And I will try hard not to waste a precious moment that could be spent cuddling.  I will, however, try to notice someone with puffy eyes.  And if the opportunity presents, I’ll buy their yogurt.