Friday, November 18, 2011

ZEB Who?

It’s been another exhilarating week on Podtburg Circle.  Last Friday we scored a cancellation slot for Ava’s follow up appointment from her E.M.U. stay, the next available slot was February so it was a hailed surprise.  On Wednesday evening as I was preparing mentally (literally making my notes) for the follow-up, the phone rang; UC Denver popped up on the caller ID.  By now I know that administration calls come from Children’s Hospital, only doctor’s phone from UC Denver numbers.  I picked the call up immediately as I figured it was a cancellation for the next day.  To my surprise, it wasn’t.

“Hi, is this Ava’s mom?”
Yes, this is Amanda, Ava’s mom.

“This is Dr Gallagher, I seen Ava back in April, do you remember me?”
Yes, I do.

“I’m calling because I have some news in regards to one of the test we ran at that appointment and I see I missed you on campus a couple of times in October.  Is this a good time?”
Yes.

“We have identified a sequence change in Ava’s ZEB2 gene that we are unable to interpret without you and her dad’s DNA.  We have never seen this before; your daughter has been on my mind.”
The conversation goes in depth to a level I will try to summarize, I am thankful for Dr Gallagher’s patience with me while working through the information she had.  In short, in early June the University of Chicago discovered a coding error, not previously seen before in Ava’s zeb2 mutation analysis.  There is no duplication or deletion but a sequence error with a variant of unknown significance.  They have sent it to three additional labs (Germany being the location of one), all with the same results.  She has discussed the case with all experts world-wide and everyone agrees that it is worth exploring.

She has reservations, it wouldn’t surprise her if it wasn’t Mowat-Wilson; Ava would be the first MWS diagnosis with C.V.I., but understanding the role the variation plays would be helpful to understanding more about Ava and genetics in general.  Usually a disease is identified that they cannot locate a gene for.  This is quite opposite of that.

The University of Chicago has offered to test Joe and me for free.  Yesterday I met with Dr G on campus; we had a nice informal appointment in the waiting room of the 3rd floor out-patient pavilion.  She had a chance to take a gander at Aliza, explain a bit more to me, and see Ava in action after her med change.  I picked up the spit DNA kits & paperwork from the Lab in Chicago.  She also told me I could expect a genetic counseling appointment when the results were back, likely with Dr Scharer…he was Ava’s first m.d. visiting the genetics/metabolic clinic as an infant.
What does this mean?

*If Joe has the variant and I don’t…Mowat-Wilson Syndrome will be diagnosed
*If neither of us have the variant…all this talk about single and double changes, very complicated stuff that no one is really sure about yet (especially me listening to the scientist on the phone).

*If both of us do, it probably means very little, potential polymorphism (benign sequence change, we all have them).  We will be the first to explore this theory by giving our sample.

We should know in 4-weeks what the general consensus is.  With the holidays, I am shooting for the first of the year at best.  We had a phone call today to set up another epileptologist appointment in late February so I would guess we will know more by then.
For all you science geeks out there here is a taste of the report:

DNA sequence analysis of the ZEB2 gene in this patient demonstrated a nucleotide change in exon 8, c.3444C>T, which does not result in an amino acid change, p.Y1148Y.  This sequence change does not appear to have been previously described in patients with Mowat Wilson syndrome and also does not appear to have been described as a known polymorphism (benign sequence change) in the ZEB2 gene…mutations and deletions/duplications have been identified in approximately 98% of patients with Mowat-Wilson syndrome.  Our interpretation is based on the current understanding of the genetics of Mowat-Wilson syndrome.

Yesterday I left them my spit sample; today Joe dropped his off with a courier on the North Campus.  He and Aliza are on their way to Rio Rancho, NM to honor his lovely Grandma Marie Jaksha’s life.   She passed peacefully over a week ago after a long and blessed life.  Aliza and she never met so my heart is warmed by the fact Aliza gets to pay her respects and spend time getting to know the New Mexico Jaksha’s a bit more.
Someday I will post what this means to me, it is a complicated issue in general.  For now, my spirit has been lifted knowing folks are starting to take notice, trying to explain Ava better so she can hopefully feel better.
Looking forward to sharing my 2011 gratitude soon!

2 comments:

Summer said...

This is really interesting Taz! I hope that something will turn up some answers and some help for Ava!!!! Hugs to you guys!!!

TherExtras said...

You are very good at providing a means to more understanding even if us neuro-plebes are unable to fully comprehend. Thanks, Amanda!

Sympathy to your family on the loss of Grandma Jaksha.

Barbara