Improving the diagnosis of nebulin-based nemaline myopathy

Dr Carina Wallgren-Pettersson and her team are developing techniques that can be used as a fast and reliable genetic diagnostic service for people with nemaline myopathy. This research will improve the genetic diagnosis of nemaline myopathy and give scientists a better understanding of how nebulin mutations cause the condition.



Dr Wallgren-Pettersson’s team has developed a new microarray (a type of genetic diagnostic method) to detect large mutations in the nebulin gene. This method specifically compares the nebulin gene from people with nemaline myopathy with the normally structured nebulin gene of people without the condition. The microarray has also been expanded to test additional genes known to cause neuromuscular conditions. The microarray is now being used for diagnostic purposes and DNA samples from more than 200 families have been analysed. Importantly, the microarray has revealed new mutations in the nebulin gene and in another gene that causes nemaline myopathy.

The second new method, called a nanopore assay (a method to read long sequences of DNA) is being developed to increase the length of specific sequences of DNA that can be measured. This is important because of the huge size of the nebulin gene. These advances bring new methods to identify condition-causing mutations in people with nemaline myopathy and provide important information of how the condition can be inherited.

The researchers have also studied the interactions of normal nebulin and actin. These two proteins bind to each other and help the muscle to contract. They will now study how mutations in nebulin interfere with this interaction and how it affects the muscle. This method is a key tool to gain a better understanding of the disease mechanisms, which is important for the development of potential therapies.

What are the aims of this research project?

The most common cause of nemaline myopathy is mutations in the nebulin gene. The huge length of this gene makes it difficult for geneticists to pinpoint the mutations that are responsible for the condition. Furthermore, many people with nebulin-based nemaline myopathy have two different mutations within the giant nebulin gene. This makes genetic analysis even more challenging.

The aim of this project is to develop methods for a fast and reliable genetic diagnostic service for people with nemaline myopathy. Dr Wallgren-Pettersson and her PhD student, Lydia Sagath, will develop a combination of laboratory techniques that can identify disease-causing mutations in the nebulin gene. They have collected DNA samples from people with nemaline myopathy, in addition to clinical information about their condition. They will investigate whether there are correlations between the genetic and clinical data, e.g. whether specific nebulin mutations give rise to certain clinical symptoms.

Why is this research important?

This research will improve the genetic diagnosis of nemaline myopathy and give scientists a better understanding of how nebulin mutations cause the condition. This knowledge is important for the development of treatments in the future.

How will the outcomes of this research benefit people with nemaline myopathy?

Patients taking part in this project will often receive a genetic diagnosis, which may be a requirement for participating in future clinical trials. Families taking part in the project will also gain knowledge about how their condition has been passed down or inherited. This may be important for prospective parents who are thinking about starting their own family.

The findings from this project will also be the starting point for research into potential therapies, which could have important benefits for people with nebulin-based nemaline myopathy.

How might your research impact on other neuromuscular conditions?

Nebulin is an important muscle protein that helps our muscles to form and function normally. It does this by binding to other proteins in the muscle. One of the techniques being developed in this project will assess how mutations affect the ability of nebulin to bind to these proteins. This will tell us more about how the proteins in our muscles work together to produce muscle contraction, and what happens if they cannot interact in the normal way. This will benefit our understanding of muscle contraction and how this might go wrong in people with neuromuscular conditions.

Grant information

Project leader: Dr Carina Wallgren-Pettersson
Institute: University of Helsinki, and Samfundet Folkhaelsan, Finland
Condition: Nemaline myopathy
Duration: three years, starting 2017
Total cost: £151,500
Official title: Development of molecular diagnostics for nebulin-caused nemaline myopathy

Further information

Read our factsheet on nemaline myopathy

Find out what other nemaline myopathy research projects we are funding

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