Heredity of Parkinsons Disease
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Date
2021
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Parkinson´s disease (PD) is an uncurable disease that has characteristic clinical manifestations including tremor, rigidity, bradykinesia and postural instability, but there can be large differences between patients regarding severity of symptoms, rate of progression and time of onset. PD nearly always also associate with a plethora of non-motor symptoms including neuropsychiatric disorders such as depression, anxiety, hallucinations as well as sleeping disorders, hyposmia/anosmia, constipation, urinary incontinence, orthostatic hypotension, cognitive decline and dementia. The onset of non-motor symptoms usually precedes motor symptoms by 12-14 years. PD is multifactorial and hence, both genetic and environmental factors impact the risk of disease, but overall age is the greatest risk factor. Idiopathic PD typically has the characteristic symptoms and age of onset that usually is after 50 years while the monogenetic PD presentation can vary greatly depending on the gene that is mutated. In this study I review the clinical manifestation, normal cellular function and believed pathological mechanism associated with 18 different genes. Known monogenic PD variants only accounts for around 5-10% of all cases of PD and every gene variant has varying degrees of penetrance. However, there is a strong relationship between gene variants and age of onset, symptoms and progression of the disease. Some gene variants lead to specific dominant symptoms which can be motor or non-motor symptoms. For example, alterations of the GBA gene is a major risk factor for PD and mutations are present in 1% of the overall population and 5% of all PD patients. It is estimated to increase the risk of PD by 20-30 times and is often associated with dementia. Carriers of mutations in the LRRK2 gene have a phenotype similar to idiopathic PD whereas mutations in the SNCA gene leads to variable phenotypes, it can be early onset typical PD, dementia with Lewy bodies and more atypical symptoms. Nonsense mutations in the DNAJC6 gene lead to very severe phenotypes while the missense mutations lead to more typical PD. Clinical presentation of patients with mutations in PRKN, PINK1 and DJ1 is usually early onset with slow progression. The identification of gene mutations contributing to development of PD has helped to understand the vulnerable biological processes and their relation to pathology which has opened for new treatment strategies that are now being investigated.
Parkinson´s disease (PD) is an uncurable disease that has characteristic clinical manifestations including tremor, rigidity, bradykinesia and postural instability, but there can be large differences between patients regarding severity of symptoms, rate of progression and time of onset. PD nearly always also associate with a plethora of non-motor symptoms including neuropsychiatric disorders such as depression, anxiety, hallucinations as well as sleeping disorders, hyposmia/anosmia, constipation, urinary incontinence, orthostatic hypotension, cognitive decline and dementia. The onset of non-motor symptoms usually precedes motor symptoms by 12-14 years. PD is multifactorial and hence, both genetic and environmental factors impact the risk of disease, but overall age is the greatest risk factor. Idiopathic PD typically has the characteristic symptoms and age of onset that usually is after 50 years while the monogenetic PD presentation can vary greatly depending on the gene that is mutated. In this study I review the clinical manifestation, normal cellular function and believed pathological mechanism associated with 18 different genes. Known monogenic PD variants only accounts for around 5-10% of all cases of PD and every gene variant has varying degrees of penetrance. However, there is a strong relationship between gene variants and age of onset, symptoms and progression of the disease. Some gene variants lead to specific dominant symptoms which can be motor or non-motor symptoms. For example, alterations of the GBA gene is a major risk factor for PD and mutations are present in 1% of the overall population and 5% of all PD patients. It is estimated to increase the risk of PD by 20-30 times and is often associated with dementia. Carriers of mutations in the LRRK2 gene have a phenotype similar to idiopathic PD whereas mutations in the SNCA gene leads to variable phenotypes, it can be early onset typical PD, dementia with Lewy bodies and more atypical symptoms. Nonsense mutations in the DNAJC6 gene lead to very severe phenotypes while the missense mutations lead to more typical PD. Clinical presentation of patients with mutations in PRKN, PINK1 and DJ1 is usually early onset with slow progression. The identification of gene mutations contributing to development of PD has helped to understand the vulnerable biological processes and their relation to pathology which has opened for new treatment strategies that are now being investigated.
Parkinson´s disease (PD) is an uncurable disease that has characteristic clinical manifestations including tremor, rigidity, bradykinesia and postural instability, but there can be large differences between patients regarding severity of symptoms, rate of progression and time of onset. PD nearly always also associate with a plethora of non-motor symptoms including neuropsychiatric disorders such as depression, anxiety, hallucinations as well as sleeping disorders, hyposmia/anosmia, constipation, urinary incontinence, orthostatic hypotension, cognitive decline and dementia. The onset of non-motor symptoms usually precedes motor symptoms by 12-14 years. PD is multifactorial and hence, both genetic and environmental factors impact the risk of disease, but overall age is the greatest risk factor. Idiopathic PD typically has the characteristic symptoms and age of onset that usually is after 50 years while the monogenetic PD presentation can vary greatly depending on the gene that is mutated. In this study I review the clinical manifestation, normal cellular function and believed pathological mechanism associated with 18 different genes. Known monogenic PD variants only accounts for around 5-10% of all cases of PD and every gene variant has varying degrees of penetrance. However, there is a strong relationship between gene variants and age of onset, symptoms and progression of the disease. Some gene variants lead to specific dominant symptoms which can be motor or non-motor symptoms. For example, alterations of the GBA gene is a major risk factor for PD and mutations are present in 1% of the overall population and 5% of all PD patients. It is estimated to increase the risk of PD by 20-30 times and is often associated with dementia. Carriers of mutations in the LRRK2 gene have a phenotype similar to idiopathic PD whereas mutations in the SNCA gene leads to variable phenotypes, it can be early onset typical PD, dementia with Lewy bodies and more atypical symptoms. Nonsense mutations in the DNAJC6 gene lead to very severe phenotypes while the missense mutations lead to more typical PD. Clinical presentation of patients with mutations in PRKN, PINK1 and DJ1 is usually early onset with slow progression. The identification of gene mutations contributing to development of PD has helped to understand the vulnerable biological processes and their relation to pathology which has opened for new treatment strategies that are now being investigated.
Description
Medicīna
Medicine
Veselības aprūpe
Health Care
Medicine
Veselības aprūpe
Health Care
Keywords
Parkinsons disease, monogenetic Parkinsons disease, clinical manifestation, Parkinsons disease, monogenetic Parkinsons disease, clinical manifestation