Abnormal Numbers Of Chromosomes
When a mistake occurs as a cell is dividing, it can cause an error in the number of chromosomes a person has. The developing embryo then grows from cells that have either too many chromosomes or not enough.
In trisomy, for example, there are three copies of one particular chromosome instead of the normal two . Trisomy 21 , trisomy 18 , and trisomy 13 are examples of this type of genetic problem.
Trisomy 18 affects 1 out of every 7,500 births. Children with this syndrome have a low birth weight and a small head, mouth, and jaw. Their hands typically form clenched fists with fingers that overlap. They also might have birth defects involving the hips and feet, heart and kidney problems, and intellectual disability. Only about 5% of these children are expected to live longer than 1 year.
Trisomy 13 affects 1 out of every 15,000 to 25,000 births. Children with this condition often have cleft lip and palate, extra fingers or toes, foot abnormalities, and many different structural abnormalities of the skull and face. This condition also can cause birth defects of the ribs, heart, abdominal organs, and sex organs. Long-term survival is unlikely but possible.
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.
Genes And Frontotemporal Dementia
Frontotemporal dementia , originally called Picks disease, is a rarer type of dementia mostly affecting people under the age of 65 years. The symptoms of FTD can be quite varied but include changes that mostly affect behaviour or language. There are different types of FTD, and these are likely to have different causes.
Some people with FTD have a family history of dementia and the condition may be inherited in some of these families. For behavioural variant FTD, a third to half of people could have a family history. This figure is thought to be much lower for other types of FTD.
Overall, around one in ten cases of FTD are thought to be caused by a faulty gene passed down in families. Several genes have been found that can cause these inherited types of FTD, including:
Mutations in the MAPT gene can cause the tau protein to behave abnormally, forming toxic clumps that can damage brain cells. We still need to understand more about how mutations in progranulin and C9ORF72 cause the disease.
The C9ORF72 gene can cause people to develop motor neurone disease, FTD or both conditions, and may affect members of the same family differently.
In cases of FTD that are not caused by faulty genes, the risk factors are not yet fully understood, and research is ongoing.
Is genetic testing available for frontotemporal dementia?
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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.
Here Are Some Environmental Factors That May Play A Role
“Some environmental factors that may contribute to PD include head trauma or exposure to certain chemicals or toxins,” said Beck. “For example, paraquat, a widely used commercial herbicide in the U.S., and trichloroethylene , a solvent used in many industries and the most common organic contaminant found in groundwater, have both been linked to PD. However, some people may have a genetic makeup that makes them more vulnerable to the effects of these substances than others.”
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What Is The Number 1 Cause Of Parkinson’s
“Scientists believe the disease is caused by an interaction of genes, environmental and lifestyle influences, so we are not able to narrow it down to one top cause,” says Beck. “One thing that all people with PD have in common is they have lost and continue to lose dopaminergic neurons in their brain. We are currently trying to understand why that happens and how we stop it.” Keep reading to learn about how your genetics may play a role.
Ibuprofen May Reduce Risk Of Parkinson’s
Study Shows the Painkiller May Have Benefits in Preventing Parkinson’s Disease
Feb. 17, 2010 — People who take ibuprofen may be nearly 40% less likely to develop Parkinson’s disease, according to a new study.
Researchers found the pain reliever was the only one in the popular class of nonsteroidal anti-inflammatory drugs studied that had any effect on risk of Parkinson’s disease.
“Other NSAIDs and analgesics, including aspirin and acetaminophen, did not appear to have any effect on lowering a person’s risk of developing Parkinson’s,” says researcher Xiang Gao, MD, with Harvard School of Public Health in Boston, in a news release. “More research is needed as to how and why ibuprofen appears to reduce the risk of Parkinson’s disease, which affects up to one million people in the United States.”
The study, to be presented at the annual meeting of the American Academy of Neurology in April, looked at whether use of ibuprofen or other NSAIDs was associated with a lower risk of Parkinson’s disease in 136,474 men and women in the Health Professionals Follow-up Study and the Nurses’ Health Study. No participants had Parkinsonâs at the start of the study.
During six years of follow-up, 293 cases of Parkinson’s disease were diagnosed.
These effects of ibuprofen on the risk of developing Parkinson’s disease remained the same regardless of factors such as age, smoking status, and caffeine use.
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The Heart Of The Matter: Cardiovascular Effects Of Parkinsons Disease
It has long been understood that Parkinsons disease does not just cause movement symptoms, but also causes a litany of non-motor symptoms with effects throughout the body. One of the organ systems that is affected is the cardiac system, encompassing the heart, as well as the major and minor blood vessels. I received this topic as a suggestion from a blog reader and we will be discussing this important issue today. Please feel free to suggest your own blog topic.
Therapeutic Implications Of Monogenic Loci
Parkinsons disease is insidious, age-associated and chronic, and consequently a multitude of factors must come into play not only genetic. Nevertheless, the latter provide an unequivocal foundation to elucidate the molecular and cellular biology going awry. So much neuroscience is based on model systems rather than the human condition. Our continued ignorance clearly contributes to past failures in clinical trials and our inability to remedy the condition. Genetic discoveries through linkage, reveal profound insights into the mechanisms of cellular dysfunction and death in parkinsonism, and conversely in the mechanisms required for healthy aging of the basal ganglia. Although these findings are not immediately obvious or intrinsically connected within a pathway or temporal sequence of cellular events, the hope of many is that investigating the molecular consequences of these variants will provide clues as to the commonalities and/or differences in the etiology of these forms of disease. Leading on from this, it is clearly hoped that such an understanding will be directly relevant to the more common, apparently sporadic forms of disease.
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What Type Of Pain Occurs With Parkinsons Disease
The types of pain associated with Parkinsons include: ;aching or burning pain from muscles or skeleton, sharp pain from a nerve or nerve root, numbness or pins and needles pain also radiating from a nerve or nerve root, pulsing or aching pain that results from tightness or ongoing twisting and writhing movements , restlessness caused from akathisia, and sudden, sharp burning pain that occurs for no known reason.
Genes With A Possible Role In Pd
Apart from the genes causing the six monogenic forms of PD, changes in a large number of additional genes were considered PD-causative and identified by linkage analysis or a candidate gene approach. Some of these genes even attained a PARKI designation . However, as discussed in the Genetic Classification of PD section, the link of some of these genes to PD is uncertain and not confirmed. Furthermore, mutations in some PARKs cause PD that is an inconsistent or only a minor feature of a more complex phenotype or are a very rare cause of PD . In addition, mutations in synphilin-1, NR4A2/Nurr1, POLG, mortalin, and recently presenilin-associated rhomboid-like protein were considered pathogenic based on the known function or expression/protein interaction pattern of the proteins they encode. Nevertheless, they too, are now recognized as only a minor contributor to the pool of genetic PD if at all.
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Can Frontotemporal Dementia Be Inherited
Sometimes, yes. FTD is relatively rare compared with Alzheimers disease or vascular dementia, but it can be passed on directly from parent to child. A diagnosis of FTD can therefore cause a great deal of worry to someone who has children or grandchildren.;
Most FTD is not directly inherited, but about 40 per cent of people who develop the condition will have at least one close relative diagnosed with some kind of dementia. This can include FTD, Alzheimers disease or amyotrophic lateral sclerosis . In general, the greater the number of relatives who have had dementia particularly FTD or ALS the greater the chances of developing familial FTD.
Of the different types of FTD, the behavioural form is the one that is inherited most often. The type of FTD which starts as primary progressive aphasia is only rarely inherited.
There are lots of different genes causing familial FTD, each with its own pattern of inheritance. If you are concerned about either passing on an FTD gene or inheriting the disease from your parents, you can ask your GP to refer you to a genetic testing service in your area. These people are specially trained to guide you through the process of finding out whether you have a gene that causes FTD. You can also get in touch with a specialist support group at Rare Dementia Support, who can provide information and advice about how to cope with having a heritable form of FTD in your family.
Recognising The Phenotype Of Genetic Forms Of Parkinsons Disease In Clinical Practice
Posted in Clinical Review Article on 2nd Sep 2015
Parkinsons disease is a heterogeneous, neurodegenerative disorder affecting 6.3 million people worldwide and 1.2 million in Europe.1 The annual cost to Europe is estimated at 13.9 billion euro2,3 and the numbers are predicted to double by 2030.4 PD places a huge socioeconomic burden on Western economies and poses a major challenge for patients and society. Only symptomatic treatment is available. Traditional linkage analysis, gene cloning and Genome Wide Association Studies have identified several loci and genes associated with monogenic PD. The study of monogenic forms of PD may lead to the identification of new targets for pharmacotherapy and these may ultimately translate into new therapies for sporadic PD. However, treatment developed using these new technologies may only be effective for specific genetic mutations eg. kinase inhibitors for LRRK2 mutations. GWAS and linkage analysis have identified 18 Parkinsons disease loci numbered in a chronological order. This classification is imperfect as it contains both confirmed and unconfirmed loci and the causative gene remains unknown for many loci. Additionally one of the proposed loci was later found to be previously reported .5
Mutations in seven genes cause either autosomal dominant , or autosomal recessive familial PD.5 Moreover some of these genes contain polymorphisms which act as risk factors for the development of PD.6
When Should A Person Seek Genetic Testing
Genetic testing is available for some genes related to Parkinsons disease, but testing may not provide useful information to individuals.
For one thing, a wide range of genes may play a role, and it is not possible to test them all. A person may also have a relevant feature but not go on to develop Parkinsons disease.
For example, only around 0.7% of people with symptoms of Parkinsons disease have changes in the LRRK2 gene, and around 0.3% have changes in the PRKN gene, according to a 2020 review.
Finding out in advance if a young person has the gene may help them prepare for the future if there is strong evidence of a family history of the condition. However, the results are unlikely to be conclusive and may cause unnecessary anxiety.
Anyone who is interested in genetic testing should discuss the pros and cons with a doctor and consider genetic counseling if they decide to go ahead.
Candidate Gene Association Studies
The majority of efforts in the 1990s through to 2006 centered on simple, and generally small, case control candidate gene analyses. In this design a cohort of cases and controls, usually ~100200 subjects in size was typed for a single polymorphism in a candidate gene to determine if a variant was more common in cases than controls. The genes selected were usually functional candidates, and the variant selected for typing was most often one that altered an amino acid. This effort was largely unsuccessful, with the some notable exceptions.
The first indication that SNCA contained risk variants came from this type of work, with the publication of a nominal association between alleles of the REP1 polymorphism in the promoter region of SNCA and risk for disease. While this initial work was intriguing, a large number of follow up studies failed to produce a clear picture of whether this was a genuine risk locus, providing both support for and against this association. Clarity only came to this issue with the publication of a large collaborative analysis of ~5000 samples, which showed a clear association between increased risk and the long REP1 alleles. This work suggests that the disease-linked alleles are associated with a 1.4 fold increase in risk for PD. As is discussed later, this story became more complicated with the advent of genome wide association studies.
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The Autosomal Dominant Forms
Mutations in two genes cause autosomal dominant forms of PD. Mutations in the alpha-synuclein gene are rare and include point mutations and whole-locus multiplications ., Duplications are detected in ~12% of the PD families compatible with autosomal dominant inheritance. Triplications and point mutations are exceedingly rare: the Ala53Thr mutation has been found in a few families of Greek ancestry; Ala30Pro and Glu46Lys have been detected so far in single families, of German and Spanish origin, respectively. The brain pathology is characterized by abundant -synuclein-positive neuronal inclusions , but the associated clinical spectrum is broad, ranging from classical PD to more atypical and aggressive phenotypes , and resembling diffuse Lewy body disease or multiple system atrophy. The patients with SNCA duplications often display a classical PD phenotype, whereas the more rare cases carrying triplications display more severe phenotypes, in keeping with a direct relationship between SNCA gene dosage and disease severity., However, wide clinical variability is observed also within the same family. The SNCA mutations are usually higly penetrant, but instances of reduced penetrance have been reported for the SNCA duplication.
What Causes Parkinsons
Currently there is no known cause of Parkinsons or understanding of why some people develop Parkinsons and not others. This is the reason Parkinsons is often referred to as Idiopathic Parkinsons.
There are many theories as to the causes of Parkinsons and it is generally thought that multiple factors are responsible.;
Through research, our understanding of the possible causes of Parkinsons is increasing all of the time. Areas of current research include: ageing, genes, environmental factors, chemical exposure and viruses.;
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