Spatax Meeting - Papers, Day 3

This is the fourth and final instalment of the papers presented, this time the third day. As previously, the papers were a mix of HSP and Ataxia papers, and I focused on paying most attention to the HSP papers.

The first of the sessions was on functional studies, with more focus on HSP than Ataxia.

Full post index:
Overview: http://hspjourney.blogspot.co.uk/2016/06/international-meeting-on-spastic.html
Papers Day 1: http://hspjourney.blogspot.co.uk/2016/07/spatax-meet-papers-day-1.html
Papers Day 2a: http://hspjourney.blogspot.co.uk/2016/07/spatax-meeting-papers-day-2-part-1.html
Papers Day 2b: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-papers-day-2-part-2.html
Papers Day 3: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-papers-day-3.html
Posters 1: http://hspjourney.blogspot.co.uk/2016/08/spatax-meeting-poster-sessions-part-1.html
Posters 2: http://hspjourney.blogspot.co.uk/2016/09/spatax-meeting-poster-sessions-part-2.html

Evan Reid (http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/reid) talked about discovering some unifying mechanisms within HSP. He noted that that there are more than 50 genes affected by HSP, but there are a few common themes across these different genes, including cell membrane traffic. Evan noted that Spastin (the protein produced by the Spast gene, and affected by SPG4) has two different forms (or isoforms). There is some redundancy between these forms, but both need to be affected for HSP to show.

Tim Newton (http://www.cimr.cam.ac.uk/research/principal-investigators/principal-investigators-q-z/reid) talked about age of onset for HSP, noting that the HSP's with point mutations tend to have later onset than those with deletion mutations. He also reported that the effects of HSP were bigger when the deletions were larger, particularly if the deletion extended to the next gene along.

The second session focused on diagnostics.

Stefania Magri (https://www.researchgate.net/profile/Stefania_Magri) gave an overview of next generation sequencing (NGS) panels, noting the potential for mis-diagnosis, given that there are some overlaps between HSP and Ataxia, with the genetic test giving the opposite result to a clinical diagnosis in some cases. A joint HSP/Ataxia panel was suggested.

Sara Morais (https://www.researchgate.net/profile/Sara_Morais3) said that 40-60% of  families have unknown diagnoses. They checked 98 families against the most frequent HSP genes and identified the gene in 21 of these.

Lydie Burglen (https://www.researchgate.net/profile/Lydie_Burglen) reported similar information about testing for ataxias, indicating that a gene panel would only cover about 20% of diagnoses. 

As before, I realise that it is on a very different level to my normal posts. I know I've just used a lot of terms that I dont normally use, and I've just kept this post to the points which I perceived to be most important.

My key takeaway points from this session are:

• Gene panels - with the panels of the common genes still only covering some 20% of the tests, that leaves some 80% without a clear diagnosis. I perceive this to be important - particularly letting people know the likelihood of a match, and defining a process after this.
• The genetic mutations for HSP (and Ataxia) can vary in size, and potentially affect more than one gene, with potentially more than one consequence. 

The question which came through my mind at this time was: how do the dominant transmission cases start - its fair enough to note that they transmit from one generation to the next, but they must start somewhere.