April 21, 2003

Abnormal Chromosomes Might Be Risk Factors for ALS

Researchers have found abnormalities in the chromosomes — the strands of DNA in which genes reside — in several people with sporadic amyotrophic lateral sclerosis.

ALS attacks muscle-controlling nerve cells in the spinal cord, often leading to paralysis and respiratory failure within three to five years of diagnosis. About 10 percent of cases are hereditary, but the other 90 percent are sporadic, of thus far unknown cause.

The new findings, reported in the April 22 issue of Neurology, suggest there might be a genetic component to at least some sporadic cases.

Researchers led by Thomas Meyer of Charité University Hospital in Berlin used blood samples to examine the chromosomes of 85 German patients with sporadic ALS. Five of the patients (6 percent) had chromosomal rearrangements — either a reshuffling of DNA between two chromosomes, or a flipped-over piece of DNA within a single chromosome. These types of abnormalities are believed to occur in less than one-tenth of 1 percent of the general population.

The chromosome or pair of chromosomes affected was different for each patient.

Healthy family members of four patients had the same abnormalities, indicating that the abnormalities were inherited and not secondary to ALS. A few of the relatives had advanced past the age of ALS onset in the patients, suggesting they might never develop the disease.

Robert Brown, director of the MDA/ALS Center at Massachusetts General Hospital in Boston, said the study “is very important because it suggests that chromosomal disruption may underlie some cases of sporadic ALS.” The presence of chromosomal abnormalities in people without the disease fits with a long-held theory that sporadic ALS might arise from a combination of genetic and environmental factors, he said.

“The next step is to confirm these [findings] in an independent study of as many or more patients,” he said. Since 1997, his lab has been collecting blood samples and detailed histories from ALS patients in an attempt to identify genetic and environmental triggers of ALS. Click here to see the trial description.

If chromosomal aberrations prove to be a common feature in sporadic ALS, they could be used to pinpoint specific genes that affect ALS risk. Similar aberrations — easier to detect than small changes in DNA — have been used to identify genes involved in other diseases. Already, the German researchers have found that the jumbled pieces of chromosome from their patients contain many genes with important functions in nerve cells.