Monday 28 November 2011
New advances in FSHD research
On November 7 and 8, eighty scientists met in Boston, Massachusetts, to share the latest results from their research on facioscapulohumeral muscular dystrophy (FSHD). This conference is hosted annually by the American FSH Society. Andreas Leidenroth, a Muscular Dystrophy Campaign-funded PhD student researching FSHD in Nottingham, attended the conference and here he reports on two important highlights presented at the meeting.
Most cases of FSHD are caused by a genetic deletion on chromosome 4. This reduces the number of a DNA repeat called D4Z4 from several dozen repeats to fewer than 11. Every repeat of D4Z4 contains a copy of the DUX4 gene. It is thought that the reduction in D4Z4 repeat number 'relaxes' the DNA, which results in the undesired production of DUX4 gene messages. These messages are believed to cause muscle weakness and degeneration.
New insight into the cause of FSHD
Dr Stephen Tapscott from The Fred Hutchinson Cancer Research Centre, Seattle presented his group's latest research into DUX4 gene messages and the DUX4 protein. There is good evidence that the DUX4 protein can bind to DNA, and it is thought that it can regulate a number of different genes by interacting with them. Using a new technique called "ChIP-Seq", Dr Tapscott's laboratory searched the whole human genome to look for genes that may be under the control of DUX4.
For the first time, this important study identified more than a thousand different genes that DUX4 might be interacting with. Dr Tapscott's laboratory also confirmed that a number of these "DUX4-target" genes changed their activity when DUX4 was blocked. This suggests that at least some of the gene "targets" identified by the ChIP-Seq experiment are directly under DUX4 control.
The identification of DUX4 target genes will greatly aid future research into how DUX4 exerts its toxic effect on muscle. This could lead to the identification of new therapeutic approaches that could be developed for FSHD.
Genetic test for rare type of FSHD - FSHD2
In some cases, patients do not have a D4Z4 deletion, but the DNA is relaxed by some other (still unidentified) mechanism. Such patients are sometimes described to have "FSHD2". Scientists think that while their D4Z4-relaxation is caused by a different mechanism, they produce the same toxic DUX4 messages and therefore have the same problems with their muscles as patients who have the deletion.
Dr Richard Lemmers from the Leiden University Medical Centre, The Netherlands presented his work on FSHD2. His research group has developed a very reliable laboratory test to detect the DNA relaxation in FSHD1 and FSHD2 patients. The test can clearly distinguish patients with FSHD1 and FSHD2 from patients with other muscular dystrophies.
This is important because patients without the D4Z4 deletion currently do not get a definite genetic diagnosis. In fact, patients with FSHD2 are often misdiagnosed as having other types of muscular dystrophy such as limb-girdle muscular dystrophy. The improved laboratory test will therefore allow clinical geneticists to give patients with FSHD2 a clearer diagnosis.
Further information
More information about facioscapulohumeral muscular dystrophy.
More FSHD research news.
Read about the FSHD research we fund.
If you have a question about this, or any other research please email us: research@muscular-dystrophy.org.
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