Whole exome sequencing analyzes all of a person’s genes, in both the nucleus (which contains most of a cell’s genetic material) and mitochondria (energy powerhouses of cells, containing a little genetic material). It can find misspellings or mutations of the genes.
Kiran’s results gave us no well-known diagnosis. No clear genetic disorder was identified.
A gene mutation was found in a gene that has only been newly described – in the past two years – and is currently under a lot of research. The geneticist and counselor both feel this mutation may be our diagnosis for Kiran, but there is not enough evidence at this time for it to be definitive.
He has a missense mutation – a SINGLE letter misspelled – in a gene called RAB11B. Neither my gene nor Kiran’s dad’s gene had this misspelling, so it is sporadic and unique to Kiran’s DNA. He did not inherit it from us.
No other significant gene variants were discovered in the nuclei. One misspelling was found in Kiran’s mitochondria DNA. This misspelling was also present in me. Both the geneticist and counselor feel this is benign and have no concerns. They do not feel it gives Kiran a diagnosis.
Back to RAB11B. Mouse studies have been done. It appears this is an important gene for brain expression and heart function. It is important in cell signaling as well. When the gene is not working, the mice have abnormal movement and neuronal function and show a defect in the nervous system.
Two – TWO – patients who have undergone whole exome sequencing have the same misspelling in RAB11B. Both have very similar features as Kiran – neurodevelopmental disorder, brain abnormalities, variable vision problems, delayed speech and motor skills, low muscle tone, and small head size.
What does this all mean? (And yes, I am writing this blog going straight off of notes I was taking during the phone call with the genetic counselor.)
1) We have ruled out more common, well-known neurological genetic syndromes. This is rare. We don’t know much about it. (Story of Kiran’s life)
2) This gene is important in brain pathways and heart function. Two other patients have been identified that have similar features to Kiran. But. We don’t know the full spectrum of features that might be associated with this misspelling.
3) We don’t know how rare or common variants in this gene are – there just isn’t enough data out there at this time. We don’t know if certain mutations can cause certain outcomes. We don’t know the prognosis. We don’t know if/that there are any medical management changes that should be made. There is just a lot we don’t know.
4) This is a change unique to Kiran’s DNA. This is not inherited from either of us. It is not something that would have occurred with any environmental influences during pregnancy. (I had to ask, and yes I choked up – It’s not my fault.)
5) The gene is currently under research, so the chances we learn more is really high. The genetic counselor felt really good about this – that we will likely know more in the future. Kiran may even get to be a part of some research. Who knows? Maybe we will fight to get them to name the eventual diagnosis after him. (He is the coolest kid in the world, after all, and apparently 1 of only 3 patients known to have this mutation of this gene.)
That might have been a lot of repeat information. My brain isn’t able to fully process this at this time, so I really am just regurgitating – and expounding, a little, off my notes. It is better than a negative result. But it just doesn’t give us…much. Yet.