A single gene mutation can cause multiple diseases 同一基因缺陷 可能引發不同疾病

Wed, Nov 27, 2013 - Page 11

Can a single gene defect cause two different diseases? When one 45-year-old woman started suffering from dementia, Chang Gung Memorial Hospital conducted tests and discovered that she also had two collateral blood relatives and one direct blood relative who had dementia. Genetic testing showed evidence of abnormalities in C9orf72 (chromosome 9 open reading frame 72), which was the cause of this familial frontotemporal dementia (FTD).

In another case of a person with amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, Chang Gung Memorial Hospital discovered the same gene mutation in the patient’s hereditary history. The patient was also 40-something when he started suffering from muscular dystrophy, but he showed no signs of dementia, exhibiting how the same genetic mutation in C9orf72 can cause two distinct degenerative neurological diseases.

Yeh Tu-hsueh, a neurologist at Chang Gung Memorial Hospital’s Taipei Branch, says that in 2011 researchers from the US National Institutes of Health discovered that disease-causing mutations in the gene C9orf72 could cause dementia, as well as the motor neuron disease ALS. The hospital subsequently joined this research team in conducting related international research.

This disease-causing gene mutation can be found in around 25.1 percent of patients with early-onset familial FTD, Yeh says, adding that 37.6 percent of patients with familial ALS also exhibit the mutation.

The female patient, for example, was only 45 years old when she started suffering memory loss and physical impairment. At the time, her family discovered that she had lost interest in daily life. These changes in cognitive ability and personality made it difficult for her to maintain amicable relations with coworkers. By the age of 49, she suffered muscular dystrophy and joint contractures in her limbs, so that she had to rely entirely upon others to take care of her. Aside from her, one of her parents and two of her collateral relatives had the same disease. In the other family, four out of six siblings exhibited symptoms such as dementia and personality changes.

Chen Jou-hsien, director of movement disorders in the Division of Neurology at the hospital, says that 65 is the average age when dementia usually occurs. The patient who started suffering from dementia in her 40s, for example, or even someone in their 50s, would be considered to have early-onset dementia, Chen says, adding that he recommends getting tested for genetic abnormalities in such cases.

Aside from clinical genetic testing, Chen says that with degenerative nerve diseases, including dementia, Parkinson’s disease and ALS, now that it is known that one gene can cause two different diseases, it means that a new research avenue is available and shows that in the future it might be possible to find a mechanism explaining the degenerative process in humans.

(Liberty Times, Translated by Kyle Jeffcoat)