Shortening of Telomeres Linked to Muscular Dystrophy Onset

Shortening of Telomeres Linked to Muscular Dystrophy Onset

A recent study that was published in the journal Nature Structural & Molecular Biology reveals that the shortening of the telomeres (a process that is linked to the aging process of the organism) is associated with an increased gene expression associated with FSHD (Facioscapulohumeral muscular dystrophy). FSHD, also known as Landouzy-Dejerine, is an autosomal dominant inherited form of muscular dystrophy which affects the skeletal muscles of the face (facio), scapula (scapulo) and upper arms (humeral). Symptoms of the disease appear by the age of 20, even though other muscular dystrophies show symptoms earlier during childhood. Furthermore, only 1 in less than 20,000 patients who carry the genetic mutations responsible for FSHD, will eventually develop the disease.

The main author of the study and the leader of the research team from the UTSW (University of Texas Southwestern) Medical Center, in the United States, professor Woodring Wright, affirms that these results could explain the late onset of the disease and the fact that only a very small number of patients develop the disease, even if they are carriers for the mutated genes.

Muscular Dystrophy

Telomeres are regions of repetitive sequences of nucleotides found at the end of each chromatid. Their role is to protect the chromosomes from either external deterioration or  fusion with other chromosomes. The genes found in the proximity of the telomeres are usually inactive. With age, the telomeres shorten, thus affecting the expression of the proximity genes. This effect is currently known as TPE (telomere position effect). Due to the fact that the gene responsible for the development of FSHD is in the vicinity of a telomere, it is usually inactive. However, due to the shortening of the telomeres, the gene, named DUX4, changes its expression.

Professor Wright and his research team managed to clone the muscle precursor cells from patients suffering from FSHD and their healthy siblings. They discovered that there was a difference between the lengths of the telomeres. According to the results of the study, the expression of the DUX4 gene dramatically increased as the length of the telomeres decreased. This suggests that if a patient either has telomeres that shorten at a slower rate, or has longer telomeres, will most likely never develop the disease, even if they carry the DUX4 gene.

The shortening of the telomeres could also explain why the disease has such a late onset. The research team from UTSW are already planning future studies that will focus on the link between FSHD onset and telomere length. DUX4 is rather close to the telomeres, being only 25 to 60 kilobases away, however, scientists also discovered that the shortening of the telomeres affects the FRG2 gene as well, found at 100 kilobases away. This discovery is an indication that the telomere position effect could affect many other genes. Researchers affirm that in the near future, physicians will take the length of the telomeres into consideration when diagnosing these muscular dystrophies and other genetic disorders linked to the shortening of telomeres.