More genetics questions for you guys

Junebug060609

For starters, is a 405KB deletion a big one?

My other question is regarding this sentence in the email I got from DS's doc (I asked her to email me the results after we spoke). 

"In order to further evaluate clinical relevance, parental metaphase FISH analysis
utilizing interval specific BAC probes is necessary to determine whether
this alteration represents a familial variant or a de novo change more
likely to be clinically significant."

I get that they want DH and I tested to find out if it was inherited or a 'fluke' thing.  I'm confused though about the clinical references.  Is one method of having such a deletion better/worse than the other?  From what I can find on Google the phrases are basically referring to things that impact his daily life.  This deletion for sure seems to be impacting his/our daily life (it's known to be linked to developmental delays and apraxia of speech...he's was dx'd with dev delays more than a year ago and I suspected apraxia before I was told it is common with his deletion). I'm still trying to figure out if autism is common with this deletion...  Clearly it seems to be present in DS's case, but I'm curious if he's an anomaly or the norm. 

Assembly_Reqd

It doesn't really matter if the deletion is inherited or not. It's more how that deletion affects that particular person. Remember that you also have environment and circumstances that also play a role. If you or your DH has the same deletion, I wouldn't bet on your child being affected in the same way. One of Nate's deletions is considered a syndrome. According to research based on other patients, he should have about 11 "issues". He only has 7 from the list. He does not have tethered cord, seizures, chiari 1 malformation or ventriculomegaly/hydrocephalus. 

A deletion smaller than 5Mb (Mega bases) is considered a microdeletion. The size of the deletion does not necessarily correlate with affectedness. The location of the deletion and what genes are missing or partially missing is what determines what issues or syndromes your child will have. 

Nate has three deletions on chromo 1. One is 5.3Mb (19 genes) one is 836kb(20 genes) and the third is 274kb (2 genes). You can see that the 'size' of the deletion is not proportional to the amount of genes involved.

HTH

EmAre

I think that because the world of genetics is so new, it's really difficult to find a straight answer. So many experts seem to have varying opinions on what is considered significant and what isn't.

My daughter's deletion is ~665kb and she has been diagnosed with a micro deletion. One neurologist that we spoke with said anything under 500kb was considered insignificant. But I have spoken with parents of children with changes >500kb who felt they were significantly impacted by their abnormality.

We also saw an endocrinologist who felt that if our daughter's deletion came from either me or my husband, and we were not affected by the deletion at all, than it was unlikely the deletion was the cause of her issues. However, if the change was de novo (which her's was) than it would be likely that the abnormality was what caused her various problems.

I think it would be worth seeking out some Facebook groups specific to your child's deletion and see if many of those with the same genetic change exhibit similar symptoms.

Best of luck!

Junebug060609

Hehe, I can tell you this 405 seems pretty significant. Could be a lot worse, but it for sure impacts a lot in his life.