Five to 10 percent of ALS cases are hereditary, and researchers have identified several genes that are linked to the disease. In sporadic ALS, researchers have identified several genetic risk factors for the disease, but much remains to be discovered about the role genetics play in the disease.
This study examined the chromosomes of 85 people in Germany with sporadic ALS. Five people had chromosomal abnormalities, for a rate of 5.9 percent.
"Since the normal rate of chromosomal abnormalities in healthy people is .05 to .1 percent, this is a very high rate for people with ALS," said study author and neurologist Thomas Meyer, MD, of Charité University Hospital in Berlin. "It's very unlikely that these two conditions could appear together that often and not be related."
The finding suggests that these chromosomal rearrangements are a previously unknown risk factor for sporadic ALS, Meyer said.
Researchers don't know how the chromosomal rearrangements contribute to ALS. "They may result in the disruption or alteration of susceptibility genes that haven't been identified yet," Meyer said. "Another possibility could be that an underlying mechanism of ALS that has yet to be determined could promote the development of these chromosomal abnormalities."
Meyer said that studying chromosomal rearrangements has played an important role in identifying genes involved in other diseases. "In ALS, this approach could be particularly helpful," he said. "Because the disease involves so many genes and since it mainly occurs sporadically, identifying potential genes by looking at the entire genome for links has been very difficult."
Meyer said this research underscores the need for a systematic genetic analysis of patients with ALS and other neurodegenerative diseases.
The researchers also tested the patients' family members for the chromosomal abnormalities. Family members of four of the five patients had the same chromosomal abnormality as their family member but showed no symptoms of the disease. This shows that the chromosomal abnormality was transmitted by a parent who was a carrier, Meyer said.
"Since three of the family members were older – in their 60s and 70s – this suggests that more than one factor may be necessary for the disease to manifest itself," Meyer said. "This adds weight to the current theory that sporadic ALS is caused by multiple factors, including modifying genes and environmental agents."
Four of the five patients had typical ALS that was clinically indistinguishable from other ALS patients. The fifth patient had a known variant of the disease that occurs along with frontotemporal dementia, a degenerative disorder that causes loss of brain cells in the frontal and temporal lobes of the brain. However, Meyer noted that one additional patient with this variation of the disease was tested and did not have chromosomal abnormalities.
None of the five patients had any anatomical abnormalities or history of loss of pregnancy by miscarriage or stillbirth, which could indicate other types of chromosomal abnormalities.
The study was supported by the VERUM Foundation in Munich and the German Genome Programme.
The American Academy of Neurology, an association of more than 18,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer's disease, epilepsy, Parkinson's disease, autism and multiple sclerosis. For more information about the American Academy of Neurology, visit its web site at www.aan.com.
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Neurology