More on mutations

So I know both of my son's GJB2 genes have mutations. What does this mean on a molecular level? Do his cells not make Connexin 26 at all? Or do they all come out wonky?

It seems that this depends on the mutation. And surprisingly enough, having wonky Cx 26 proteins might cause more problems than having none at all.

Genetics is a field of science which still holds a lot of mysteries, despite the fact that all DNA is made of just 4 chemicals. These are called A, G, C, T (for Adenine, Guanine, Cytosine, Thymine), and the whole genetic code for a person can be stored as a (rather large) collection of books with those 4 letters repeated again and again. 

Three of these letters together (called a codon) are enough to send a message to your cells. In fact that seems to be how the DNA is read, three letters at a time. Just like how a computer reads bytes, which is a group of eight 1s or 0s. There are 64 different 3-letter combos (4 x 4 x 4). 61 of these create molecules (amino acids) and the other 3 mark the end of a protein.

You can also think of it in terms of lego. Each codon (three letters) causes the cell to make a different brick, these all stick together in a specific way until you finish with your toy. Except the bricks are called amino acids and the toys are proteins. 

The c.35DelG that I carry is the most common mutation associated with hearing loss. Its ugly name actually describes a lot about it. The 'c' at the start means its a mutation in coding DNA  - this is DNA that is used specifically for making proteins. 'Del' means something has been deleted. In this case it's a Guanine, hence the 'G'. The 35 tells us where the deletion is - 35 codons in.
This turns the 35th codon into something called a stop codon - a 3 letter combo that basically tells your cell to stop making this protein. So it ends up just making the first part of Cx26, then stops.
This picture probably shows what normal Cx26 looks like:

And this one probably shows what my mutated Cx26 looks like:

Fairly shite isn't it? Looks like it does feck all. It is in fact completely useless. Mutations like this, that leave the protein doing nothing, are called 'knock out' mutations. Knock-out mutations in Cx26 seem to always cause hearing loss, with no other effects.
However different mutations can change how Cx26 works, and this leads to other issues. I'll look at this...... next time.


Terminology

• Nucleotide A molecule with a particular structure. The four building blocks of DNA (Adenine, Guanine, Cytosine, Thymine) are nucleotides.
• Codon A group of 3 nucleotides in a row on a DNA strand
• Amino Acid A molecule with a particular structure. They can be built through the use of codons and joined together to form proteins
• Protein One of the molecules constituting a large portion of the mass of every life form and necessary in the diet of all animals, composed of 20 or more amino acids linked into one or more long chains. Proteins include such specialized forms as collagen for supportive tissue, hemoglobin for transport, antibodies for immune defense, and enzymes for metabolism