Genetic Testing For Parkinsons Disease
Similar to other complex diseases, the reason a particular person develops Parkinsons disease is likely a combination of genetic makeup and environment. In most people, the genetic contribution to disease development may be due to a number of different genes and the interactions between them. For only a very small percentage of people with PD, about 10%, the disease can be attributed to a single abnormal gene. Figuring out the identity and contributions of all the different genes that play a role in disease development is a very hot topic in PD research today.
Current Genetic Testing Practice
The vast majority of participants ordered genetic testingon ten or fewer patients in the 12 months prior to completing the study.Furthermore, most participants reported that only ten or fewer of theirpatients reported undergoing direct-to-consumer testing . Inaddition, participants reported that few of their patients received genetictesting either in research projects that returned results to patients or in research projects that did not returnresults to patients. For either type of study design , more than 80% of clinicians reported ten patients or fewer who hadgenetic testing. In contrast to genetic testing, DNA banking under researchprotocols was more prevalent. Thirty percent of respondents reported banking DNAfor 11 or more patients in the past year . Consistent withresponses citing limited genetic testing and reporting, caring for patients withknown pathogenic variants was rare among survey respondents. Only 5.5% and 4.9%of responders reported providing care to more than ten known LRRK2 or GBApatients, respectively. In total, participants reported providing care for 490known LRRK2 carriers and 402 known GBA carriers. Providing care for patients withknown Parkin , PINK-1 , SNCA , and VPS35 pathogenic variants was anecdotal .
Genetics Of Parkinson’s Disease Risk
Risk for Parkinson’s disease is influenced by genetics. In fact, the disease is associated with genetic variants in many genes. Two of the best studied genes associated with Parkinson’s disease are called LRRK2 and GBA. There are other genesand variants that have also been linked to Parkinson’s disease, but most of these genetic variants are either rare or have only a smalleffect on risk.
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Genetic Testing For Parkinson’s Disease And Related Disorders Minutes
Dr. Michael WatsonAlthough the terms are often used interchangeably, testing and screening have two distinct uses. Genetic testing involves the analysis of symptomatic individuals or those with a family history, whereas screening uses a population-based approach. Ethical issues associated with both of these forms of testing include test validation and test performance. The intended use of the test should be specific it might therefore be helpful to articulate the intended use as if FDA approval were required.
There are 2 stages through which a genetic test can be translated into clinical practice.
Stage 1: includes population-based research to establish scientific links between genes and diseases. Laboratories would not have to be approved under the Clinical Laboratory Improvement Amendments of 1988 because they do not report to the families, but Institutional Review Boards should oversee patient involvement. The FDA regulates manufactured devices and drugs, and provides guidance for informed consent requirements, but genetic “home brew” tests often fall through the regulatory gap. Moreover, while CLIA regulates how laboratories practice, it does not address the issue of clinical validity.
Stage 3: involves the development of practice standards for tests that are found to be adequate and of utility at Stage 2. This involves the development of guidelines for testing and who should be tested.
Dr. Quaid outlined the types of genetic testing as:
Genetic Classification Of Pd
In the current PD genetics nomenclature, 18 specific chromosomal regions, also called chromosomal locus, are termed PARK , and numbered in chronological order of their identification . In addition to being an incomplete list of known PD-related genes, this classification system, unfortunately, has a number of inconsistencies. It comprises confirmed loci, as well as those for which linkage or association could not be replicated . The causative gene has not yet been identified for all of the loci, nor do all of the identified genes contain causative or disease-determining mutations . Finally, one locus, PARK4, was designated as a novel chromosomal region associated with PD but was later found to be identical with PARK1 . It is noteworthy that some of the loci have been identified by genetic linkage analysis in large families, some based on the known function of the protein product of the gene they contain, yet others have been established by genome-wide association studies performed on a population level. A list of the PARK PD-related genes and loci is given in , along with their clinical classification, inheritance pattern , gene , status , and mode of identification.
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Is Genetic Testing Worth It
In my humble opinion, we still have a long way to go when it comes to bipolar and genetic testing.
At this stage of the game, undergoing this kind of test is not going to give you any concrete answers. Sure, it might tell you that you are at risk for the illness. But, you could probably assess this risk with the help of a mental health professional by examining your family history and taking an honest inventory of your symptoms.
It would be way cool if genetic tests worked kind of like pregnancy tests. You pee on a stick, and a few words in a little window seal your fate. Instead of pregnant or not pregnant, the test would say bipolar or not bipolar. We are a long way from getting these kinds of results.
If you think you would benefit from taking a genetic test for bipolar disorder, you can always give it a go.
Just a word of caution: you may end up more confused about your situation than when you started. While genetic testing may help some people, I think speaking to a medical professional is your best bet for getting a proper diagnosis when it comes to having bipolar disorder.
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How The Hd Gene Causes Huntingtons Disease
The genetic problem of Huntingtons disease, the CAG repeats, causes an abnormality in the production of a protein called the huntingtin protein. It is not completely clear exactly what this protein does in people who do not have Huntingtons disease. What is known, however, is that in Huntingtons disease, the huntingtin protein is longer than usual and becomes prone to fragmentation . It is believed that this elongation or the resulting fragmentation may be toxic to nerve cells in the brain that affects mood and behavior.
The specific region of the brain impacted by Huntingtons disease is the basal ganglia, a region deep in the brain that is also known to be responsible for Parkinsons disease. Like Parkinsons disease, Huntingtons disease is characterized by movement problems, but Huntingtons disease is more rapidly progressive, is fatal, and dementia is the most prominent symptom of the disease.
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Genetic Testing: Whom To Test And How
The answer to the question of who should be tested is not trivial. To date, no formal testing guidelines have been developed by the Movement Disorder Society or any other PD alliance group. Out of all monogenic forms, mutations in LRRK2, Parkin, and PINK1 are the most likely to be encountered in clinical practice. In the following scenarios, genetic testing might prove useful to minimize further patient workup, to clarify treatment approaches, and/or to assist with future family planning: juvenile-onset PD irrespective of family history early-onset PD with atypical features and/or a positive family history of this disease or late-onset PD with a strong family history of PD . Guidelines published by the European Federation of the Neurological Sciences recommend screening LRRK2 for mutations in Europeans showing dominant inheritance of PD, testing for the LRRK2 p.G2019S mutation in familial and sporadic cases of PD in specific populations, and analysis of Parkin, PINK1, and DJ-1 in patients aged < 35 yr with recessively inherited PD .
Q Is Genetic Testing Available On The Nhs
Yes, genetic testing is available but the directly inherited genetic forms of Parkinsons are very rare and there are currently no treatments that can prevent the condition. We would usually consider genetic testing for people who develop the condition early or who have a strong family history, with several people in the family affected.
If you are considering genetic testing its important that you fully understand what it means before its carried out.
Some people may find it helpful to talk to a genetics specialist before proceeding with genetic testing. We would recommend that all patients and or families with a positive genetic test have access to genetic counselling to help them understand the possible implications.
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Research Into Genes And Parkinsons
Our major effort now is understanding how mutations in these genes cause Parkinsons disease, says Dawson. SNCA, the gene responsible for making the protein that clumps in the brain and triggers symptoms, is particularly interesting.
Our research is trying to understand how alpha-synuclein works, how it travels through the brain, says Dawson. The latest theory is that it transfers from cell to cell, and our work supports that idea. Weve identified a protein that lets clumps of alpha-synuclein into cells, and we hope a therapy can be developed that interferes with that process.
Targeting Parkinsons-Linked Protein Could Neutralize 2 of the Diseases Causes
Researchers report they have discovered how two problem proteins known to cause Parkinsons disease are chemically linked, suggesting that someday, both could be neutralized by a single drug designed to target the link.
Identification Of New Genes And Risk Factors For Pd
New PD-linked genes or PD risk factors can be identified by gene mapping or candidate gene approaches. Gene mapping in human diseases is the localization of genes underlying the clinical phenotypes of the disease on the basis of correlation with DNA variants , without the need for prior hypotheses about biological function. Genetic mapping methods include linkage analysis and genome-wide association studies. Alternatively, based on their known function, levels of expression, or mode of interaction , some genes can be considered plausible candidates, and as such, tested for in cohorts of patients.
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Genetics Of Huntingtons Disease
Gene coding is made of a sequence of nucleic acids, which are molecules on our DNA that code for the proteins that our bodies need for normal function. The specific coding deficit in Huntingtons disease is an increase of the number of repetitions of three nucleic acids, cytosine, adenine, and guanine, in the region of the first exon of the HD gene. This is described as a CAG repeat.
Normally, we should have about 20 CAG repeats in this particular location. If you have less than 26 repeats, you are not expected to develop Huntingtons disease. If you have between 27 and 35 CAG repeats, you are unlikely to develop the condition, but you are at risk of passing on the disease to your offspring. If you have between 36 and 40 repeats, you may develop the condition yourself. People who have over 40 CAG repeats are expected to develop the disease.
Another observation with this genetic defect is that the number of repeats often increases with each generation, a phenomenon known as anticipation. So, for example, if you have a parent who has 27 CAG repeats in the region responsible for Huntingtons disease, you could have a sibling with 31 repeats, and your sibling may have a child who has more repeats. The importance of anticipation in the genetics of Huntingtons disease is that a person who has more CAG repeats is expected to develop symptoms of the disease earlier than a person who has fewer repeats.
Is It Worth Getting A Genetic Test For Dementia Risk Variants
Genetic tests for dementia risk variants are not recommended. This is because knowing whether someone has genetic risk variants does not mean knowing for certain whether they will develop dementia. A person who has risk variants may have a higher risk of developing dementia, but even someone at a higher risk may never develop the condition.
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Genetic Testing For Single
Genetic testing for single-gene causes of dementia is available through the NHS.
There are two different types of genetic testing diagnostic testing and predictive testing. These are used for different purposes.
People affected by dementia can also use genetic testing for family planning.
Diagnostic testing for dementia
Genetic Testing Shows Promise For Providing A Bipolar Diagnosis And Identifying Risk
I would gladly give blood, pee in a cup, get a brain scan, or undergo any other type of medical testing to get a definitive diagnosis. That way, I couldnt argue with myself and pretend it doesnt exist as I often do. I am pretty sure people with diabetes dont question their condition probably because they have undeniable proof that it exists.
But, what if there was a test that could immediately diagnose a person with bipolar disorder? Imagine how this would change the lives of millions of people who struggle with mental health issues!
Some researchers say we are on the verge of having access to such a test. With the latest developments in genetic testing, more and more people are using this method as a way to determine their risk for bipolar disorder.
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People Who Already Have Pd: Should I Get Tested And What Do I Do With The Results
Up until recently, even people with PD with a very extensive family history of PD would not necessarily receive genetic testing because there were no clear uses for the results. There has been research directed at figuring out whether PD caused by or associated with certain mutations have particular clinical characteristics . However, there remains so much variability in clinical characteristics even among people with the same PD mutation, that there are still no clear practical implications in knowing whether a PD patient harbors a particular mutation. There is also, so far, no difference in treatment or management of PD whether or not the patient harbors one of the known mutations. That may change however, with the advent of clinical trials that target particular mutations.
There are two genes that have received particular attention recently because medications are being developed that target those with mutations of these genes.
GBAis a gene that increases the risk of developing PD. The gene encodes for the GBA enzyme, a protein used by the body to break down cellular products. Having two abnormal GBA genes causes Gauchers disease, which is characterized by the buildup of these cellular products resulting in fatigue, bone pain, easy bleeding and an enlarged spleen and liver. When a person inherits only one abnormal gene, he or she does not develop Gauchers disease, but does incur a small increased risk of PD. Most people with one mutated GBA gene do not develop PD.
For Parkinsons Patients Genetic Testing May Open Possibilities
Physicians have had little incentive to order genetic tests for their Parkinsons disease patients, although evidence suggests that up to 15% of these cases may be genetic.
Mutations in several different genes increase the risk of Parkinsons disease, says Roy N. Alcalay, MD, MS, the Alfred and Minnie Bressler Associate Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons and a neurologist at NewYork-Presbyterian/Columbia University Irving Medical Center. Until recently, we rarely offered genetic testing for people with Parkinsons because the benefit had been unclear.
But recent studies have shown that genotype can help better estimate the rate of disease progression in Parkinsons. And as new drugs designed for people with specific Parkinsons genes have entered clinical trials , Alcalay realized the calculus has changed.
From our own genetic studies, I realized many people were eligible to enroll in such trials, but they didnt know it because nobody told them about their genetic status, Alcalay says. I wanted to find a simple, ethical way to offer Parkinsons patients information about their genotype if they are interested.
Alcalay, the principal investigator of PDGENEration, talked to the CUIMC Newsroom about how the program may help support the development of personalized therapies for Parkinsons patients.
Why is now the right time to start genetic testing in Parkinsons disease?
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What Are The Benefits Of Predictive Testing
Having the test can be helpful for the following reasons:
- It can remove the anxiety of not knowing especially as the person approaches the age at which any symptoms of dementia are likely to start.
- It can give the person the option of entering into a clinical trial.
- It can help with family planning.
When Should Genetic Testing Be Done
Your physician may suggest it if your Parkinsons diagnosis comes at a young age , if multiple relatives in your family history have also been diagnosed with the same, or if you are at high risk for familial Parkinsons based on your ethnicity .
However, what is the benefit of having the testing done at the present time? The information may be important for family planning for some individuals although as I said even if the gene is passed on it does not necessarily equal development of the disease. The risk, though, is higher in dominant genetic mutations versus recessive ones, on average if a person has a first-degree relative with Parkinsons their risk of developing the disease is 4 to 9 percent more than the general population.
Keep in mind that currently for the person being tested, there is no change in the treatment of their Parkinsons disease based on genetic findings. In the future, however, when there are treatments to slow down the onset of the disease or to prevent it from developing at all, then the identification of those people at risk will be very important.
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