The rarest of the rare - a diagnosis, definitive

"We found it. We found it," our genetic counselor blurted out. "It's recessive."

And I started to cry. And then she started to cry. So we cried.

For the last 34 years I have been carrying a rare mutation on Chromosome 22, gene ALG12. My husband has spent his 32 years on this Earth carrying the only known mutation of its kind, also on gene ALG12. This causes, specifically and definitively, Congenital Disorder of Glycosylation type 1g - a rare and fatal form of a rare disease, caused by rare mutations on rarely affected genes. There are 500 known cases of glycosylation in the world. Our type - 1g - has only 10 (now 11) known cases. In all cases recorded in medical literature, not one of the babies survived.

"Literally, there is a one in a million chance you carry a mutation on this gene and then for the two of you to find each other..." the GC said.

Factor in the 25 percent chance of affected pregnancy - multiply that by two - and you have some really big numbers and some really sad statistics.

So I hold the exome data from our second son in my hand - a scant six pages of heartache and wait and worry. The printout tells the tale of a little boy who would never be born, who would never grow or play or cry, a little boy who held mutations on five other genes for four far more common autosomal recessive disorders and was a carrier for the dominant Cornelia DeLange syndrome - and the rarest thing, the thing no one in Vegas would have worried about statistically - ended his life and our dreams for him and his brother.

We spent all of yesterday trying to wrap our heads around this new information. First, I think, is the stunning realization that the exome found the cause. We had a 25 to 30 percent chance of diagnosis. Of the 30 exomes reviewed by the doctors at our hospital, ours is one of the few to offer such helpful information.
Then, out of the doctor's office and at a ironic hipster coffee shop, we wrapped our hands around mugs of warm chai and wrapped our heads around our future. The autosomal recessive 25 percent has always been our "best case scenario," though we've lost this gamble twice so far.
IVF with PGD is a possibility for us now. Cost is a huge factor, and so is the time frame. It would take weeks to begin the process and for doctors to begin the PGD probe that would find potentially skewed genes in our embryos. But, that said, I'm not sure I would be ready for a pregnancy any sooner than that, either.

I think the one thing that is most notable to me at the end of the exome is the blanket of peace that seems to be tucked around our little family now. The diagnosis in no way brings my babies back to me. It doesn't change any outcomes. But knowing what we know now, saying that we have the information, that we took this to the wall for our boys, is like balm on my still-raw heart. I have so struggled with this unknown killer - was it me? Was it my husband? How could this happen with no prior family history? My questions are answered and there is a calm in my mind and a stillness in my soul that I welcome with all my heart. This is peace. The decisions we made as new parents of lost boys were the right decisions. We have been validated in all the ways every parent hopes to be validated. No one can tell us otherwise.

This is not the end of our genetic journey, by the way. Far from it.
Baylor will now retrieve our first son's banked DNA for comparison to our second son's exome, to confirm - once and for all, that this is the gene mutation that killed both boys. This will put a diagnosis once and for all on the syndromatic physical evidence from MRI's, ultrasounds, genetic testing and autopsies on both boys.
We have been approached by the lead geneticist at our hospital, as she would like to write a medical paper - to be published in a medical journal - about our boys and our genes and our exome. We have also consented to an interview with a major metro newspaper to tell our exome story. This only furthers what I hoped to do with this blog in the first place - to shed a beam of light on the medical and very emotional journey of the exome - what it means for people, for families like mine, who never dreamed they could be so touched - and so saved - by science. I hope that the brilliant minds at Baylor College of Medicine and all the other major and minor players in the world of Sanger sequencing keep congratulating each other on the successes of the exome process, but also take a minute to remember that the results are as emotional for their patients as they are significant for science. At the end of the day, exomes are for people, not just scientists. Exomes may save lives, but they also heal souls.

Keep an eye on this blog space - I'm not done with this journey.