Molecular Testing

We drew more blood from Niko to find the exact two mutations in her DNA that caused I-Cell.  This was done for a couple reasons. 

1)  To confirm that this is Mucolipidosis type II disease (a.k.a. I-Cell), and not type III or type II/III.  (There are actually types I and IV as well, but they are very very different from Niko’s condition.)  The difference between type II and III and II/III is a matter of 10 to even 50 years difference in life expectancy, as well as the severity of destruction to the body.  This also gives us an idea of care/management for her as we move on down the road.  Type II is the most severe.  The test confirmed that Niko has type II.  I’ll explain her specific mutations in detail below.     

2)  To find the exact mutations for reproductive reasons.  This is for future children, future grandchildren, our siblings’ reproductive screening, cousins’, etc.  Now that they know what to look for, they can detect I-Cell with up to 99.9% accuracy by means of CVS, amnio or genetic embryo implantation, the most accurate being the amnio.  Mila can get her blood tested when she’s 18 years old to see if she’s a carrier.    

Niko’s blood sample was sent to Greenwood Genetics Center in South Carolina, where they know a great deal about I-Cell.  We were lucky that they were able to find the two mutations (in some cases, they are unable to do so).  I’ll explain the DNA protein mutations in layman’s terms here.

The first one is what’s called a “frame shift” mutation or “deletion”.   The sequences of your DNA are written in groups of threes.  The DNA strands contain very specific messages to be read and then function according to those instructions.  For example let’s say the message is (THE) (RED) (DOG) (ATE).  In Niko’s case, two of those letters are deleted.  If you remove the H and E from the word THE, you get the following jumbled message that makes no sense, which is a frame shift.  (TRE) (DDO) (GAT) (E..).  So the instructions make no sense.  The proteins are not instructed to move to the proper locations thereby leading to excess storage of proteins in her cells.

This first mutation is the classic I-Cell mutation. 

Her second mutation is a “stop-change” and incorrect lettering mutation.  In even more simple layman’s terms, her strands are misspelling phrases.  I read in the report that the exact letter that was wrong is a “T”.  Instead of the correct letter “R”, she has a “T” in its place.  Added to that, she’s got periods or stops in the instructions.  So instead of a continuous message, there are erroneous stops placed.

This second mutation is an undiscovered mutation.  They have not recorded this specific mutation before.  Which of course launched me into a panic thinking that we are on a new painful journey to discovering her true condition.  But before I was able to get carried away with this new fear the geneticist said, that based on the severity of the second mutation, Niko does have I-Cell.  Furthermore, he says that without even looking at the molecular testing results, he can say with all certainty by looking at Niko that she’s got I-Cell (ML type II). 

This geneticist has seen one other I-Cell patient and maybe five ML type III patients.  In fact, he did see an additional case of I-Cell, but that fetus was so severely affected that it was not compatible with life and died before being born.       

I’ve settled more into this seat now.  It’s not a comfy seat.  The springs are all busted, rusted, the cushion’s deflated and… well… it’s a pain in the ass.  I’m not happy about it; I don’t think I’ll ever be.  But I love this little girl.  And I love my family.  I am making a pledge to myself, and my little clan, that we will live our lives to the fullest, that we cannot deny ourselves (or Nikola) the right to have fun and enjoy this world.