New mutations causing congenital myopathies

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Professor Francesco Muntoni and his colleagues at Imperial College and the Hammersmith hospital have found nine novel mutations that can cause congenital myopathies. This result was published in the prominent journal, Brain, earlier this year.


  • New mutations causing congenital myopathies
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New mutations causing congenital myopathies

The congenital myopathies are a group of conditions that includes central core disease, multi-minicore myopathy and nemaline myopathy. They are characterised by the presence of specific features that can be seen in a muscle biopsy. There are differences between each of the congenital myopathies but given the large range of variability of symptoms in the conditions it is thought there may be some overlap and common features between them.

It is thought that mutations in the gene coding for a protein called Ryanodine Receptor 1 (RYR1) may be responsible for some forms of congenital myopathy. RYR1 is a calcium-release channel that is located in a specialised part of the cell. It allows the flow of calcium out of a store so that it can bind to specific proteins in the muscle, allowing the muscle to contract.

Professor Muntoni and colleagues studied the RYR1 gene in 44 patients from 28 different families. They searched the gene for mutations and in the 44 patients found 25 different mutations, nine of which were new. Of the mutations that they found, there was a mixture of dominant (only one copy of the mutated gene is needed to cause disease) and recessive (both copies of the gene must have a mutation in order for a person to be affected) mutations.

In addition to characterising the mutations, Professor Muntoni and colleagues found a new mechanism that allowed mutations to cause disease. They provided evidence that some of the mutations, although recessive were still able to cause disease when only one copy was present. Generally, if a mutation is recessive, you need to have two mutated copies of the gene before the disease manifests. The researchers found that in those affected individuals who had inherited one normal and one mutated copy of the gene – which would not normally cause disease – only the mutant copy was being expressed. The normal gene was being “silenced”, thus allowing the disease to present.

The characterisation of these mutations, in the RYR1 gene, allows clinics to carry out much more focussed screening if an individual has the typical features of a congenital myopathy. Being able to screen the gene for mutations and understanding more about the mechanism causing the disease, clinicians will be able to offer a more accurate diagnosis for patients as well as provide much greater information on the prognosis of the condition. This allows people to plan for any changes in their physical wellbeing that might occur during the course of the disease.

Further information and links

Find out more about congenital myopathies.

The paper referred to in the above article was published in the journal of neurology, Brain.  Brain is subscription only so the original article is not freely available. The article itself is written in medically technical language with no summary in layman’s terms.

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