Inherited neuromuscular disorders (NMDs) are a very large and varied group of genetic diseases that cause degeneration of the muscles and/or the nerves that control movement. More information about the disorders covered in the NMD-Chip project can be found here.
Finding out exactly which mutation (mistake in the genetic code) is affecting a patient is very important. It allows predictions to be made about how the condition might progress and the optimal treatment plan can be made.
However, NMDs can be caused by mutations in any one of hundreds of genes so a precise genetic diagnosis can require testing each gene one at a time until the right one is found. This is highly complex and time consuming. Tests can take up to a year with the current technologies. Because of this as many as 30-40% of patients remain without a genetic diagnosis.
The aim of the NMD-Chip project is to design, develop and test new tools known as ‘chips’ which can test all the genes known to be involved in causing NMDs in one go. This will be cheaper and quicker than the one gene at a time approach, giving results within a week.
How it works
DNA carries all of the genetic code required to make, operate and maintain your body. DNA exists in two long strands - one strand is a mirror image copy of the other. The two strands wind together in a helix so that the genetic code on one strand matches up and attaches to the genetic code on the other. Because of this ability to match up, one piece of DNA can be used to ‘fish for’ its matching piece.
If scientists know the mutation they are looking for, they can put the matching code onto a small piece of glass called a ‘chip’ and use it to test a DNA sample from a patient. If the patient’s DNA contains the mutation, their DNA will bind to the chip in that exact place.
The really exciting thing about gene-chips is that the DNA code for more than 2 million mutations can be put onto the same chip, each one known to cause a different form of a neuromuscular disease. It’s a bit like a fishing rod with 2 million different hooks!
This means that a patient’s DNA can be tested for all these mutations in one go. In the past this would have meant thousands of separate tests in the laboratory meaning a much longer wait for a genetic diagnosis.
The project is designing chips for the diagnosis of mutations already known to cause Duchenne/Becker muscular dystrophies (DMD/BMD), limb girdle muscular dystrophies (LGMD), congenital muscular dystrophies (CMD), and hereditary motor-sensory neuropathies or Charcot-Marie-Tooth neuropathies (CMT). These are described as "known-gene chips".
Discovering new gene mutations
Not all genes responsible for neuromuscular disorders have yet been discovered, and an estimated 30 to 40% of patients are left without a genetic diagnosis even once all known genes have been tested. To address this, the NMD-chip project is also developing chips to test for mutations which we suspect may play a role in causing NMDs. These are called "candidate-gene chips".