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.