Navigation Links
'Rare' brain disorder may be more common than thought, say Mayo Clinic scientists
Date:12/25/2011

JACKSONVILLE, Fla. -- A global team of neuroscientists, led by researchers at Mayo Clinic in Florida, have found the gene responsible for a brain disorder that may be much more common than once believed. In the Dec. 25 online issue of Nature Genetics, the researchers say they identified 14 different mutations in the gene CSF1R that lead to development of hereditary diffuse leukoencephalopathy with spheroids (HDLS). This is a devastating disorder of the brains white matter that leads to death between ages 40 and 60. People who inherit the abnormal gene always develop HDLS. Until now, a definite diagnosis of HDLS required examination of brain tissue at biopsy or autopsy.

The finding is important because the researchers suspect that HDLS is more common than once thought and a genetic diagnosis will now be possible without need for a brain biopsy or autopsy. According to the studys senior investigator, neurologist Zbigniew K. Wszolek, M.D., a significant number of people who tested positive for the abnormal gene in this study had been diagnosed with a wide range of other conditions. These individuals were related to a patient known to have HDLS, and so their genes were also examined.

Because the symptoms of HDLS vary so widely — everything from behavior and personality changes to seizures and movement problems — these patients were misdiagnosed as having either schizophrenia, epilepsy, frontotemporal dementia, Parkinsons disease, multiple sclerosis, stroke, or other disorders, says Dr. Wszolek. Many of these patients were therefore treated with drugs that offered only toxic side effects.

Given this finding, we may soon have a blood test that can help doctors diagnose HDLS, and I predict we will find it is much more common than anyone could have imagined, he says.

Dr. Wszolek is internationally known for his long-term efforts to bring together researchers from around the world to help find cases of inherited brain disorders and discover their genetic roots.

Dr. Wszoleks interest in HDLS began when a severely disabled young woman came to see him in 2003 and mentioned that other members of her family were affected. The diagnosis of HDLS was made by his Mayo Clinic colleague, Dennis W. Dickson, M.D., who reviewed the autopsy findings of the patients uncle, who had previously been misdiagnosed as multiple sclerosis, and subsequently, Dr. Wszoleks patient and her father. All members of the family had HDLS.

Dr. Dickson had identified other cases of HDLS from Florida, New York, Oregon and Kansas in the Mayo Clinic Florida brain bank and knew of a large kindred in Virginia with similar pathology, based upon a presentation at the annual meeting of the American Association of Neuropathologists. With concerted efforts, Dr. Wszolek and collaborators at University of Virginia were able to obtain DNA samples from the Virginia kindred. Dr. Wszolek also sought other cases, particularly those that had been reported in the neuropathology literature, and he was able to obtain samples from Norway, the United Kingdom, Germany and Canada, and other sites in the U.S. He and his team of investigators and collaborators have since published studies describing the clinical, pathologic and imaging characteristics of the disorder, and they have held five international meetings on HDLS.

In this study, which included 38 researchers from 12 institutions in five countries, the studys first author, Rosa Rademakers, Ph.D., led the effort to find the gene responsible for HDLS. Her laboratory studied DNA samples from 14 families in which at least one member was diagnosed with HDLS and compared these with samples from more than 2,000 disease-free participants. The gene was ultimately found using a combination of traditional genetic linkage studies and recently developed state-of-the art sequencing methods. Most family members studied — who were found to have HDLS gene mutations — were not diagnosed with the disease, but with something else, thus emphasizing the notion that HDLS is an underdiagnosed disorder.

The CSF1R protein is an important receptor in the brain that is primarily present in microglia, the immune cells of the brain. We identified a different CSF1R mutation in every HDLS family that we studied, says Dr. Rademakers. All mutations are located in the kinase domain of CSF1R, which is critical for its activity, suggesting that these mutations may lead to deficient microglia activity. How this leads to white matter pathology in HDLS patients is not yet understood, but we now have an important lead to study.

With no other disease have we found so many affected families so quickly, says Dr. Wszolek. That tells me this disease is not rare, but quite common. He adds, It is fantastic that you can start an investigation with a single case and end up, with the help of many hands, in what we believe to be a world-class gene discovery.


'/>"/>

Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

Related medicine news :

1. ICU Patients at Risk for Rare Heart Rhythm Problem
2. reco jeans Supports Children With Rare Diseases
3. Scanning for skin cancer: Infrared system looks for deadly melanoma
4. Genetic Disease Foundation Encourages Americans to Know Their Genes at KnowYourGenes.org in Observance of World Rare Disease Day
5. Genetic cause discovered for rare bleeding disorder
6. Benefits of Osteoporosis Treatments Outweigh Possible Risk of Rare Femoral Fractures
7. Kids With Rare Condition Lack Racial Prejudice
8. Guillain-Barre Syndrome Very Rare After H1N1 Vaccine
9. Renowned Researcher Joins Children's National Medical Center to Help Conquer Rare Diseases
10. Touchstone Saunas Goes Online to Provide Premium Quality Infrared Saunas
11. Drinking While Pregnant Tied to Rare Leukemia in Offspring
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/29/2016)... ... 2016 , ... Memorial Healthcare System Graduate Medical Education ... that it has received accreditation for its residency program on Physical Medicine and ... Memorial is currently pursuing, including Pediatrics and Internal Medicine. This accreditation allows the ...
(Date:4/29/2016)... ... 29, 2016 , ... The American workforce is on everyone’s ... Most importantly, employees are the single most important asset in creating value and ... , Just under half of American workers are emotionally checked out with low ...
(Date:4/29/2016)... , ... April 29, 2016 , ... Coast Dental Fort ... 2016, at its new location in the Exchange Furniture Mall at 112 Vilseck Road ... a 50-inch Samsung Smart TV. Plus attendees will have the opportunity to meet general ...
(Date:4/29/2016)... ... 2016 , ... Mobility Designed is redefining mobility with their patent pending ... Crutch evenly distributes body weight from the elbow to the forearm. In consumer ... than with other crutches. , Co-founders Max and Liliana Younger were inspired to design ...
(Date:4/29/2016)... ... April 29, 2016 , ... Dr. Robert Mondavi, one of ... improve smiles. Cosmetic dentistry is a fast-growing field as more patients are discovering the ... to learn more about the options currently available to them and which ones might ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... Shire plc (LSE: SHP, NASDAQ: ... Financial Officer, will present at the Deutsche Bank 41st Annual ... on Wednesday, May 04, 2016, 10:00 am EDT (15:00 BST). ... the Presentations and Webcasts section of Shire,s Investor website at ... be available on this same website for approximately 90 days. ...
(Date:4/27/2016)... April 27, 2016 Oasmia ... developer of a new generation of drugs within ... survival results for Paclical/Apealea in the Phase III ... with epithelial ovarian cancer. These preliminary results showed ... combination with carboplatin versus Taxol in combination with ...
(Date:4/27/2016)... FRANCISCO , April 27, 2016 ... expected to reach USD 2.06 billion by 2022, ... Research, Inc. Increasing consumer awareness towards a healthy ... the next seven years.      (Logo: ... diet intake coupled with rising health treatment expenditure ...
Breaking Medicine Technology: