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Parkinson's disease: from genetics to clinical practice.

Clarimón J, Kulisevsky J - Curr. Genomics (2013)

Bottom Line: Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD).How and when these discoveries will be introduced into general clinical practice, however, remains uncertain.In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder.

View Article: PubMed Central - PubMed

Affiliation: Neurology Department, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

ABSTRACT
Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD). Although much research remains to be done, the main genetic causes of this neurodegenerative disorder are now partially unraveled, allowing us to feel more confident that our knowledge about the genetic architecture of PD will continue to increase exponentially. How and when these discoveries will be introduced into general clinical practice, however, remains uncertain. In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of the genetic architecture of PD. The Y axis shows the strength of genetic effects and the X axis indicatesthe age at onset of disease. Autosomal recessive genes are presented in yellow; autosomal dominant genes in blue and risk loci in green. Thesize of each circle is an approximation of the population attributable risk (PAR), that is, the proportion of PD that is ascribable to a mutationor a genetic risk variant at any gene. Percentages of PAR in genetic risk loci are based on references 56, 59 and 79. For genes related tomonogenic forms of disease (PLA2G6, ATP13A2, FBOX7, PARK2, PINK1, DJ1, SNCA and VPS35) % of PAR have limited value due to therarity of the deleterious alleles in the population and therefore the circle size represents an approximation of the % of cases due to knowngenetic causes. Relative risks for each loci are based on evidence from the PD gene database (www.pdgene.org).
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Figure 1: Schematic representation of the genetic architecture of PD. The Y axis shows the strength of genetic effects and the X axis indicatesthe age at onset of disease. Autosomal recessive genes are presented in yellow; autosomal dominant genes in blue and risk loci in green. Thesize of each circle is an approximation of the population attributable risk (PAR), that is, the proportion of PD that is ascribable to a mutationor a genetic risk variant at any gene. Percentages of PAR in genetic risk loci are based on references 56, 59 and 79. For genes related tomonogenic forms of disease (PLA2G6, ATP13A2, FBOX7, PARK2, PINK1, DJ1, SNCA and VPS35) % of PAR have limited value due to therarity of the deleterious alleles in the population and therefore the circle size represents an approximation of the % of cases due to knowngenetic causes. Relative risks for each loci are based on evidence from the PD gene database (www.pdgene.org).

Mentions: Genetic counseling and risk evaluation in sporadic, late onset PD, however, is likely of limited clinical utility at the present time. Predictive accuracy is poor due to the small effect sizes of genetic variants that have been associated with PD risk. As most of these genetic variants only explain a small proportion of the disease (Fig. 1), caution should be taken when interpreting this kind of genetic data for counseling purposes.


Parkinson's disease: from genetics to clinical practice.

Clarimón J, Kulisevsky J - Curr. Genomics (2013)

Schematic representation of the genetic architecture of PD. The Y axis shows the strength of genetic effects and the X axis indicatesthe age at onset of disease. Autosomal recessive genes are presented in yellow; autosomal dominant genes in blue and risk loci in green. Thesize of each circle is an approximation of the population attributable risk (PAR), that is, the proportion of PD that is ascribable to a mutationor a genetic risk variant at any gene. Percentages of PAR in genetic risk loci are based on references 56, 59 and 79. For genes related tomonogenic forms of disease (PLA2G6, ATP13A2, FBOX7, PARK2, PINK1, DJ1, SNCA and VPS35) % of PAR have limited value due to therarity of the deleterious alleles in the population and therefore the circle size represents an approximation of the % of cases due to knowngenetic causes. Relative risks for each loci are based on evidence from the PD gene database (www.pdgene.org).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924250&req=5

Figure 1: Schematic representation of the genetic architecture of PD. The Y axis shows the strength of genetic effects and the X axis indicatesthe age at onset of disease. Autosomal recessive genes are presented in yellow; autosomal dominant genes in blue and risk loci in green. Thesize of each circle is an approximation of the population attributable risk (PAR), that is, the proportion of PD that is ascribable to a mutationor a genetic risk variant at any gene. Percentages of PAR in genetic risk loci are based on references 56, 59 and 79. For genes related tomonogenic forms of disease (PLA2G6, ATP13A2, FBOX7, PARK2, PINK1, DJ1, SNCA and VPS35) % of PAR have limited value due to therarity of the deleterious alleles in the population and therefore the circle size represents an approximation of the % of cases due to knowngenetic causes. Relative risks for each loci are based on evidence from the PD gene database (www.pdgene.org).
Mentions: Genetic counseling and risk evaluation in sporadic, late onset PD, however, is likely of limited clinical utility at the present time. Predictive accuracy is poor due to the small effect sizes of genetic variants that have been associated with PD risk. As most of these genetic variants only explain a small proportion of the disease (Fig. 1), caution should be taken when interpreting this kind of genetic data for counseling purposes.

Bottom Line: Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD).How and when these discoveries will be introduced into general clinical practice, however, remains uncertain.In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder.

View Article: PubMed Central - PubMed

Affiliation: Neurology Department, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.

ABSTRACT
Breakthroughs in genetics over the last decade have radically advanced our understanding of the etiological basis of Parkinson's disease (PD). Although much research remains to be done, the main genetic causes of this neurodegenerative disorder are now partially unraveled, allowing us to feel more confident that our knowledge about the genetic architecture of PD will continue to increase exponentially. How and when these discoveries will be introduced into general clinical practice, however, remains uncertain. In this review, we provide a general summary of the progress in the genetics of PD and discuss how this knowledge will contribute to the diagnosis and clinical management of patients with, or at risk of this disorder.

No MeSH data available.


Related in: MedlinePlus