Tuesday, 26 March 2013

Symptoms Update - Stiffness

A few more months have passed since I last did a symptoms update. The 'problem' with a condition that acts slowly is trying to identify when something has changed. This time its more of a gut feel than a specific observation. I think it's more difficult to stand up, and I think its more difficult to stand with my legs straight for a long time.

This is a feeling over several weeks, so I dont think there are any particular circumstances which would give rise to this. My standing-with-legs-straight comment comes from one of my few multi-tasks - when I give our nearly-one-year-old his bedtime milk I stand with my legs straight, body bent over, and then move my hips to get a hamstring stretch (multi-task is stretching and feeding at same time). This has become more uncomfortable in the last week or two, and I've needed to stop the stretch for a moment and then come back to it, whereas a month or two ago I was able to hold the stretch for a whole bottle of milk.

Tuesday, 12 March 2013

Introduction to cell biology

When I met Dr Reid at Addenbrookes the other week he started to explain cell biology, and made me realise there's a large gap in my knowledge. At one level I know that I have a mutation in one of my genes and at the opposite level I know the end result of HSP. There's a huge gap in between.

My first thing to understand is the general function of a gene. In simple terms each gene carries the code to make a protein, and that protein has a particular job to do. When there is a mutation in a gene this can prevent the protein working properly. So, the importance of a mutation depends on how critical that protein is in keeping your body working.

I'll explore the protein side of things another day, and focus this time on how a mutation affects the manufacture of the protein.

Back a few months ago I found that my mutation was on Intron 12 of the Spast gene. Genes are made up of sequential blocks called Introns and Exons. There are two steps in making a protein - Transcription and Translation.

The transcription step the information in the gene is transferred into a separate molecule. The information that is needed to make the protein is from the Exon, so the transcription process involves joining all the Exon parts together and discarding the Intron parts. I'll explore the function of Introns another day. This function is called RNA splicing.

The translation step involves a Ribosome which reads the Exon sequence and uses the information to build the protein one amino acid at a time (amino acids are the building blocks of proteins). This reading and building process continues until a 'stop' instruction is reached and the protein is complete.

When there is a mutation in a gene the problem is that the Introns and Exons cannot be identified correctly, and the spliced set of Exons may contain some sections of Intron, have some parts of Exons missing or some other jumbled information. This means that the Ribosome cannot read the set of instructions correctly, and the protein is not made correctly. The body is good at checking what is made so an erroneous protein may not be made at all. If the protein is made then it may not function properly (which may mean that it works better or worse).  

I accept that this post is a bit heavy on the technical info, and I'll try and visit each of these steps again and provide some context.

Various links: