Cause of FSHD muscle disease discovered

Researchers have known for some time that patients with the hereditary muscle disease FSHD lack part of chromosome 4. But there was uncertainty about how this leads to loss of muscle tissue. Researchers at the Leiden University Medical Center (LUMC) describe in an article in Science dated 19 August how the muscle damage comes about. 

Mystery

FSDH is the world's most common muscle disease, with 1 in 14,000 sufferers. This image shows how serious the disease can be: the red areas show where a male patient has suffered muscle loss. Skeletal muscles are vital; they largely determine our ability for movement, from laughing to lifting heavy weights.

Eighteen years ago the same group discovered that FSHD - the weakening and in some cases the complete loss of skeletel muscle - is caused by a shortage of a repeated DNA structure on the end of chromosome 4. This chromosome normally contains between 10 and 100 segments, but sufferers from FSHD have 10 or less. In spite of intensive research worldwide, it remained a mystery how this deficiency resulted in muscle disease.

Explanation now found

Specialists at the LUMC, together with researchers from such centres as Seattle (US), Rochester (US) and Nijmegen, have found the explanation. Normally the end of chromosome 4 is closely packed and inaccessible. As a result of contraction, the DNA opens and is transcribed into RNA. This RNA codes for a protein that is harmful to muscle cells. RNA is normally unstable and is rapidly broken down. With FSHD patients, there is a signal on the DNA that protects RNA against breakdown. The head of the research, Professor Silvère van der Maarel from the LUMC department of Human Genetics, commented: 'As a result of this signal, the RNA is apparently present in adult muscle cells long enough to be toxic. This explains in one go all the mysteries surrounding this muscle disease.'

Symptoms

FSHD (facioscapulohumeral spierdystrophy) occurs worldwide in some 300,000 people. The first symptoms often become apparent around the age of 21, although children can also suffer from the condition. Symptoms of the disease include increasing loss of muscle strength, particularly in the face, the upper arms and the upper legs.

Link

Summary of the article in Science: A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy

(20 August 2010)