Tuesday, June 21, 2022
Tuesday, June 21, 2022
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How Is Parkinson’s Inherited

What Are The Methods Of Preventing Parkinsons Disease

Genetics of Parkinson’s Disease

As said earlier the concrete causes of Parkinsons disease are yet to be discovered. Thus, specific prevention techniques are not known as of now. However, based on few researches, some methods of prevention have seemed beneficial. They include-

Tea: Intake of caffeine and green tea may help lower the risk of developing Parkinsons disease.

Exercise: Exercise and a healthy and balanced diet keeps all form of diseases including Parkinsons at bay.

Mediterranean Food: According to few studies following a Mediterranean diet including fish, vegetables, fruits, olive oil, whole grains, nuts and seeds may lower the risk of getting Parkinsons disease.

Meat: It is important to limit dairy and red meat consumption in order to avoid Parkinsons.

Is Parkinson’s Considered A Hereditary Disease

Nope, Parkinson’s isn’t considered a hereditary disease in most people. According to the Parkinson’s Foundation, about 90% of people with the disease have no genetic link.

And while there are some genetic markers for Parkinson’s, they don’t guarantee that a person will get the disease. A genetic mutation is just one of several risk factors for Parkinson’s disease. There may also be lifestyle choices and environmental factors involved in the development of the disease. In fact, most people with Parkinson’s disease aren’t aware of any other family member with the condition, according to the National Human Genome Research Institute .

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In rare cases, Parkinson’s disease can run in families. When three or more relatives get the diseaseespecially under the age of 50, which is considered early onsetexperts believe members of the family may have a genetic predisposition to Parkinson’s.

Genetic Risk For Parkinson’s Disease

If you have a genetic mutation associated with Parkinson’s, will you get the disease? Not necessarily. Some mutations carry a greater risk, but none bring a 100 percent chance of developing Parkinson’s disease. There are many Parkinson’s risk genes where a mutation means a very small increased likelihood of Parkinson’s. Researchers are looking for other factors that either push or protect someone with a gene mutation to or from having Parkinson’s. Your doctor and/or a genetic counselor can discuss the risk associated with different Parkinson’s genes and what your results may mean for you and your loved ones.

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What Role Do Genes Play

Your genes are like your body’s instruction book. So if you get a change in one of them, it can make your body work in a slightly different way. Sometimes, that means you’re more likely to get a certain disease.

There are several genetic mutations that can raise your risk for Parkinson’s, each by a little bit. They have a part in about 1 in 10 cases.

If you have one or more of these changes, it doesn’t mean you’ll get Parkinson’s. Some people will, but many won’t, and doctors don’t know why. It may have to do with other genes or something in your environment.

Neurodevelopment Neuron Cell Differentiation And Survival

Parkinson

SNPs within loci associated with neurodevelopment, neuron cell differentiation and survival recognized as PD susceptibility factors by GWASs are listed in Table 6.

Table 6. SNPs within loci associated with neurodevelopment, neuron cell differentiation and survival recognized as PD susceptibility factors by GWASs.

CCDC62

CCDC62 was found to be related to PD susceptibility in the Nalls et al. studies conducted in 2011 and 2014 pointing out two different intron variants. The gene has a role in cell growth, estrogen receptor transactivation, cyclin D1 expression in prostate cancer cells as well as in other varieties of cancer, since its antibodies are often produced and thus detected . Until recently, it was mainly reported as related to cancer . In order to define the genes function more precisely, more functional studies are required.

RIT2

FGF20

FGF20 was proved to be associated with PD in the Nalls et al. meta-analysis , in which one intron variant within the gene with a positive association was found. More studies will have to be done to confirm this association. FGF20 is a neurotrophic factor preferentially expressed in substantia nigra pars compacta. It acts in an autocrine/paracrine manner. FGF20 regulates central nervous development and function . It plays a major role in dopaminergic neurons differentiation and survival . According to some studies, FGF20 also increases SNCA levels in dopaminergic neurons, but there is a huge discrepancy among studies .

GCH1

GPNMB

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Pathogenesis Of Parkinsons Disease

A consistent risk factor for Parkinsons disease is age . The list of putative environmental risk factors is long but, over several studies, few have shown a consistent association. Exposure to pesticides is one of the most established environmental risk factors for Parkinsons disease . The debate about the role of genes in typical, idiopathic Parkinsons disease is ongoing. The estimated proportion of patients in the general population who have at least one relative with Parkinsons disease varies from 6.4 to 10.3%, whereas studies using hospitalbased patient series report frequencies of up to 33% . The increased frequencies in clinicbased populations could truly be due to a more frequent family history amongst clinicbased patients, yet, in these patients, recollection bias for Parkinsons disease in relatives may also play a role. A large study in twins suggested strong inheritance in Parkinsons disease with onset before the age of 50 years. Beyond this onset age, however, only weak evidence for a genetic aetiology was found . Another twin study using PET neuroimaging revealed, however, disease concordance in twins regardless of onset age .

Can Parkinsons Be Genetic

According to the researches done so far it has been found that there is a possibility of some form of Parkinsons disease due to genetic mutations. However, the hereditary causes of this disease are quite rare. Around 15% of patients having Parkinsons disease are seen to have a family history of the same. It has been seen that a history of Parkinsons disease running in the family may increase the risk of a person to get it. Having a first-degree family member with Parkinsons essentially raises the risk to 3%. The statistics show that having a parent or sibling with Parkinsons disease may slightly increase the risk.

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Other Causes Of Parkinsonism

“Parkinsonism” is the umbrella term used to describe the symptoms of tremors, muscle rigidity and slowness of movement.

Parkinson’s disease is the most common type of parkinsonism, but there are also some rarer types where a specific cause can be identified.

These include parkinsonism caused by:

  • medication where symptoms develop after taking certain medications, such as some types of antipsychotic medication, and usually improve once the medication is stopped
  • other progressive brain conditions such as progressive supranuclear palsy, multiple systems atrophy and corticobasal degeneration
  • cerebrovascular disease where a series of small strokes cause several parts of the brain to die

You can read more about parkinsonism on the Parkinson’s UK website.

Page last reviewed: 30 April 2019 Next review due: 30 April 2022

How Often Does Parkinsons Run In The Family

Genetics & Parkinson’s Disease

Most Parkinsons cases have no connection to a genetic cause, but scientists have found that some gene mutations can heighten an individuals risk. Researchers believe that a better understanding of these genes may improve ways of identifying and treating the illness.

The National Institute of Neurological Disorders and Stroke reports that an estimated 15 to 25 percent of people with Parkinsons have a family history of the disorder. The Michael J. Fox Foundation for Parkinsons Research estimates that about 10 percent of cases are linked with a genetic cause.

Parkinsons doesnt stand out as a hereditary disease over and above any other chronic diseases that people deal with, says Rebecca Gilbert, MD, PhD, chief scientific officer for the American Parkinson Disease Association in New York City. But if you have a parent with Parkinsons disease, you have about a fourfold greater risk over the general population.

Still, that risk is relatively small. About 1 percent of the population over 60 has Parkinsons, according to the Michael J. Fox Foundation, and that number rises to about 4 percent for those who have a mother or father with the illness, according to Dr. Gilbert. The overall message is: Just because you have a gene linked to Parkinsons does not mean you will get the disease.

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Genetic Predispositions Reducing Differentiation Yield Of Mda Neurons

In vitro neural development was impaired in neural lines derived from patients carrying LRRK2, PRKN, SNCA, and sporadic mutations,,,. In four independent studies, the differentiation potential of neural progenitor cells derived from patients was significantly reduced, demonstrated by low yields of neurons in comparison with control lines,,,,. A recent review presented the idea that PD is attributed to significant neurodevelopmental defects, which may increase the susceptibility for disease onset. If confirmed, identifying genetic predispositions that contribute to early developmental defects in iPSC-PD may assist the development of novel PD therapies. However, these phenotypes may appear in conflict with other studies,, capable of generating functional neurons from cell lines with similar mutations. The differences could be due to varying protocols, which may be more or less stressful for the cells.

Implications For Both Research And Clinical Practice

Our current level of understanding supports the inclusion of genetic parkinsonisms in the same disease entity as PD, as long as clinical diagnostic criteria are met during life and, if available, neuropathologic criteria for PD are met.

It is unquestionable that genes involved in genetic PD can contribute to the pathophysiological substrate of PD, and that genetic PD can share common molecular, neuropathological and clinical alterations with iPD.

Major areas of research in PD genetics still need to be investigated. The discovery of new genes and variants associated with PD, the clarification of related phenotypes and the study of prodromal and preclinical phases of the neurodegenerative processes are needed. Also, research in biomarkers, including -synuclein-related biomarkers, research on innovative pharmacological compounds acting in the associated etiopathogenesis and on clinical trials design for prodromal phases are important areas of future investigation. In summary, genetic PD provided a key contribution in PD placing -synuclein at the core of PD pathophysiology, fueling basic and clinical research in pre- and post-diagnostic stages of the disease and, more recently, informing novel therapeutic strategies that are currently under clinical development and may revolutionize the care in PD.

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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.

Evidence From Epidemiological Studies

Parkinson

According to epidemiological data, genetic-related PD only accounts few PD cases. It can be argued that, with the emergence of faster and more powerful techniques to identify new genes in recent years, as next-generation sequencing, we would have had the opportunity to uncover other relevant monogenic forms or strong genetic risk factors explaining the other ~90% of iPD’ cases. Since this has not been the case, this could suggest a residual role of genetics in PD pathophysiology, and the idea that genetic forms are so particular that they do not belong in the same nosological entity with iPD. However, the current inability to find new mutations does not prevent existing genetic forms from being considered an integral part of PD. The identification of new genetic forms in rare families and the study of probable polygenic forms and epigenetic phenomena, may significantly enlarge the role of genetics in iPD.

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Genetic Role Not Entirely Known In Affected Families

Genetics very likely plays a role in all types of Parkinson’s disease. However, while having a specific combination of genetics may increase your risk of the disease, it doesn’t necessarily mean that you’ll get it.

Around 15 to 25 percent of people living with Parkinson’s have a family history of the condition, either an immediate or second-degree relation. Having one or more of these relatives will place you at slightly higher risk for Parkinson’s, but it’s still no guarantee you’ll develop the disorder.

Conversely, if you have Parkinson’s, it shouldn’t suggest that any of your kids or grandkids will get the disease either. It merely indicates that their risk is slightly above those without a family history.

In the end, most cases of Parkinson’s don’t have any known cause . While there are forms that seem to run in families, these account for a small percentage of cases roughly five to 10 percent, all told.

Recessive And Dominant Genetic Conditions

Eye colour is, in reality, a little more complex than this, but some diseases work in this way. For instance, cystic fibrosis is a recessive genetic condition that only affects people if they inherit two copies of the faulty gene.

As we can see in the diagram, if a person has one faulty gene they are not affected but are a carrier.

Should a carrier have a child with another carrier that child would have a 1 in 4 chance of inheriting cystic fibrosis.

Family trees of those with recessive condition tend to have characteristic patterns based on these probabilities, but can be very complicated as it is hard to identify unaffected carriers.

Human diseases can also be caused by dominant genes. One example of this is Huntingtons where inheriting a single version of the faulty gene is sufficient to cause the condition. The pattern within a family tree left by dominant genetic traits or conditions is somewhat easier to identify at least half of all the children of someone with a dominant inherited condition, who has children with someone without the condition, will also have the condition.

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Genes Linked To Parkinsons Disease

Theres a long list of genes known to contribute to Parkinsons, and there may be many more yet to be discovered. Here are some of the main players:

SNCA: SNCA makes the protein alpha-synuclein. In brain cells of individuals with Parkinsons disease, this protein gathers in clumps called Lewy bodies. Mutations in the SNCA gene occur in early-onset Parkinsons disease.

PARK2: The PARK2 gene makes the protein parkin, which normally helps cells break down and recycle proteins.

PARK7: Mutations in this gene cause a rare form of early-onset Parkinsons disease. The PARK7 gene makes the protein DJ-1, which protects against mitochondrial stress.

PINK1: The protein made by PINK1 is a protein kinase that protects mitochondria from stress. PINK1 mutations occur in early-onset Parkinsons disease.

LRRK2: The protein made by LRRK2 is also a protein kinase. Mutations in the LRRK2 gene have been linked to late-onset Parkinsons disease.

Among inherited cases of Parkinsons, the inheritance patterns differ depending on the genes involved. If the LRRK2 or SNCA genes are involved, Parkinsons is likely inherited from just one parent. Thats called an autosomal dominant pattern, which is when you only need one copy of a gene to be altered for the disorder to happen.

Stages Of Parkinsons Disease

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  • Stage One
  • The person will experience mild symptoms that generally do not interfere with daily activities. They may experience tremors and other movement symptoms on one side of the body and changes in posture, walking, and facial expressions can occur.
  • Stage Two
  • The person will start to experience their symptoms getting worse. Tremors, rigidity, and other movement symptoms now affect both sides of the body. Walking problems and poor posture may become more apparent and while the person is still able to live alone, daily tasks are more difficult and lengthy.
  • Stage Three
  • Stage three is often considered mid-stage. Here, the person will experience loss of balance and slowness of movements and falls are more common. The person is still fully independent, but symptoms significantly impede daily activities like dressing and eating.
  • Stage Four
  • At this stage, PD is limiting. The person will help with daily activities such as eating and dressing, so they are unable to live alone. Its possible to stand without assistance, but walking and other movements may require a walker.
  • Stage Five
  • The person will experience stiffness in the legs, making it impossible to stand or walk. The person requires a wheelchair or is bedridden and requires around-the-clock nursing care for all activities. The person may also experience hallucinations and delusions.
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    Genetic Testing And Parkinson’s

    Research suggests that a combination of genetic and environmental factors leads to the development of Parkinsons in most cases. Research continues to determine how these factors interact, and the extent to which each is involved. Current research suggests that only about five percent of cases of Parkinsons can be definitely linked to a genetic cause.

    Although there are a few families in which more than one person develops Parkinsons, it is rare for the condition to be passed from one generation to the next. Most research suggests that the condition develops as a result of genetic susceptibility and an external trigger, such as environmental chemicals. Exactly how this happens is not yet clear.

    Researchers have so far identified a number of genes that seem to be linked to Parkinsons, including the parkin, PINK1, PARK7, SNCA and LRRK2 genes. It is important to note, however, that a mutation of one of these genes does not necessarily mean that the condition will develop.

    Genetic testing for several Parkinsons genes is now quite widely available. From a medical point of view, this can help to confirm a diagnosis of Parkinsons. However, the decision to undergo genetic testing needs to be made carefully, as it may have implications for other family members. Knowing there is an increased risk of developing Parkinsons may cause unnecessary worry in people who may never go on to develop the condition.

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