Using state-of-the-art genetic sequencing techniques to find genes that cause limb-girdle muscular dystrophies 

Identifying the genes that cause a condition is essential to its effective management and treatment. Types of limb girdle muscular dystrophies (LGMD) are caused by changes in over 30 genes identified so far. However, despite continuous progress in ‘reading’ genes, called sequencing, around 50% of people with LGMD still remain genetically undiagnosed. This means there must be more genes in which changes can cause a form of LGMD.  

Professor Houlden and colleagues at UCL want to use advanced analysis of sequencing (called bioinformatics) with new techniques to sequence stretches of DNA (long-read genome sequencing) to overcome the limitations of previous sequencing techniques. This could help identify a number of causes of LGMD that relate to a person’s genetic information.  

The researchers will use bioinformatics to re-analyse strings of DNA (genetic sequences) of over 1500 people with LGMD to identify new, previously hidden genes that cause the condition. This will increase the rate of successful diagnoses. They will also sequence strings of DNA (long-read sequencing) to identify previously missed genetic causes of LGMD in another 90 families. 

Identifying genes that cause muscular dystrophies such as LGMD, and understanding how the condition progresses at a very detailed, molecular level, is essential for developing effective treatments. The researchers aim to establish new gene testing with the NHS diagnostic laboratories, which will advance and speed up the diagnosis of these conditions across the UK and beyond.