This is one of those blog posts that probably won’t interest anyone else out there, especially not very many in the 11.2-13.1 duplication region. I’m trying to figure out if there’s any link between the cause of my disorder (dopa-responsive dystonia) which is usually caused by a genetic mutation of the GCH1 gene, and the duplication that Anneliese has. I have no guilt in this search, mind you. But, if I turn out not to have the GCH1 gene mutation, I’m going to turn to looking into genes on 15q that are related to dopamine production. So far tonight, I was most interested in NIPA2.
The Dup15q family does most of their research to try to reduce the severity and delay the onset of seizures, which are a dangerous factor and have lead to a slightly high rate of sudden death among our kids. It’s a difficult topic to absorb, and the way that doctors advise us of this increased risk makes most of the group hyper aware that any night of our child’s life, they could go to sleep and never wake up. Most of us will get to see our children age. But the risk and history of alarming deaths in the Dup population seems most related to the kinds of seizures kids have, and the types of medications they are taking. Benzodiazepines are riskiest. For those parents with newly diagnosed, pre-seizure kids–sleep while you can. It’s a risk at any time, but it’s not a huge risk right now and you’ll need so much more sleep later.
Dup comes with other unique features, though, like slowing of social and intellectual development– or at least, a lack of use of social and intellectual skills which may or may not be stored in the brain. It’s painful to watch Anneliese’s discouragement when she tries new things. Also, the kids’ skeletons develop differently– cartilage areas kind of seem to be smaller so that their chests can cave in/out and their noses are short and cute. Oh, so cute! Their ears are underdeveloped so that they are low on the head and rotated to the back. Their eyes look like precious moments’ eyes, and their lips are precious little rosebud tents. I love Dup kids. They’re downright gorgeous. They have features of Autism. They love to be touched (most of them do….), and are commonly extra fond of books and music from a young age. They have features in the way they use books that make them look like they would be early readers, but as of yet, that hasn’t been the case for most of the Dup kids. It’s a goal I have for Anneliese, because she’s never very far from her bookshelf. She will sit for hours with her books, looking at each page and turning them. She will do the same with novels that have no pictures, even!
Anyway. I have another disorder entirely that is also genetic, but sometimes has an unknown genetic cause. So I’m tossing out a candidate gene for later if I need one to research. NIPA2 interests me because having lots of little changes (calls SNPs) on this gene is involved in Schizophrenia risk… and another gene that has increased risk with lots of SNPs is called COMT. COMT eats dopamine. Lots of COMT means your body is aching for more dopamine. So I’m thinking the two may be related… maybe? This is the joy of not finishing (erm, starting) grad school or med school. I have to guess a lot.
Anyway, it’s time for bed so I needed a place to pin this down that wasn’t my Facebook group for Dup15q and chose you, dear reader, to bore in addition to the facebookers who may or may not have been interested in my post on dup15q. So far I have saved myself some information that says there’s a zebrafish model of NIPA1 and NIPA2 gene expression that is used for Prader-Willi syndrome research (another disorder in the same area on this chromosome). I also saw that NIPA2 is related in some way to diabetes and magnesium intake reduces the risk of diabetes when NIPA2 has this one particular format. Since I haven’t got full-text access to studies, I haven’t yet gotten a good clue how they came to this conclusion. However, it shows that the gene is related to magnesium metabolism, neurology, and the use of insulin in the body- which includes certain organs and certain points in the brain and certain nerves and certain parts of the blood.
I like looking at each gene in depth. It gives little clues to what we’re dealing with. My daughter’s previous neurologist was rather non-plussed about current studies of gene expression- it’s all interrelated and highly variable and not direct enough in its relationships to effects to interest him. But I believe in learning, and I believe in helping. This is a clue. I love puzzles! Let’s solve the puzzle! 😀
For reference reading:
Magnesium, diabetes, NIPA2:
Microdup11.2 Gene variance in PWS
Zebrafish model team posted an explanation of their work here:
Duplications, deletions, and mutations affecting Schizophrenia: