Nicolas Dupré (MD, MSc, FRCP) is currently an attending neurologist at the CHU de Québec - Université Laval. He is the director of the Neuromuscular and Neurogenetic Disease Clinic. He is an associate professor at the Faculty of Medicine, Laval University. Dr Dupré does research in neuroscience and genomics, focusing on ataxias, ALS, HSP and Parkinson's disease.
The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highli... more The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highlights the role of the lysosome in Parkinson’s disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson’s disease have revealed multiple associated loci, including theGALClocus on chromosome 14.GALCencodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whetherGALCis the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.We first aimed to examine whether variants in theGALClocus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson’s Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson’s disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of common...
The genetic etiology of ALS includes few rare, large-effect variants and potentially many common,... more The genetic etiology of ALS includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. 335 ALS cases and 356 controls from Quebec, Canada were concurrently tested by SNP-chip genotyping and targeted sequencing of known ALS genes. ALS GWAS summary statistics were used to estimate an ALS PRS. Cases and controls were subdivided into rare variant carriers and non-carriers. Risk for ALS was significantly associated with PRS and rare variants independently, but the interaction was not significant. ALS PRS affected risk only in those not carrying a rare variant, suggesting that rare variants in ALS genes are generally sufficient for disease risk. Rather than modifying the penetrance of rare variants, ALS PRS is most informa...
ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a p... more ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious “cytokine storm. ”It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection.MethodsA 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically.ResultsFavorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8.DiscussionAs COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of A...
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient regist... more We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.
GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD)... more GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD) and tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia B. Recently, GCH1 mutations have also been reported in five patients with hereditary spastic paraplegia (HSP). In this study, a total of 400 HSP patients (291 families) from different centers across Canada were analyzed by whole exome sequencing (WES). Three patients with GCH1 variants were identified: monozygotic twins with a p.(Ser77_Leu82del) variant, and a patient with a p.(Val205Glu) variant. Both variants were predicted to be likely pathogenic. The three patients presented with childhood-onset spasticity in the lower limbs, hyperreflexia and abnormal plantar responses. Only one of the patients had diurnal fluctuations, and none had parkinsonism or dystonia. Phenotypic differences between the monozygotic twins were observed, and they responded well to levodopa treatment. Pathway enrichment analysis suggested that GCH1 sh...
BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlie... more BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.ObjectivesWe aimed to examine the association between heterozygous PRKN variants, including single nucleotide variants and copy-number variations, and PD.MethodsWe fully sequenced PRKN in 2,809 PD patients and 3,629 healthy controls, including 1,965 late onset (63.97±7.79 years, 63% men) and 553 early onset PD patients (43.33±6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. Copy-number variations were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single nucleotide variants and copy-number variations in PRKN are associated with PD risk and on...
The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highli... more The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highlights the role of the lysosome in Parkinson’s disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson’s disease have revealed multiple associated loci, including theGALClocus on chromosome 14.GALCencodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whetherGALCis the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.We first aimed to examine whether variants in theGALClocus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson’s Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson’s disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of common...
The genetic etiology of ALS includes few rare, large-effect variants and potentially many common,... more The genetic etiology of ALS includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. 335 ALS cases and 356 controls from Quebec, Canada were concurrently tested by SNP-chip genotyping and targeted sequencing of known ALS genes. ALS GWAS summary statistics were used to estimate an ALS PRS. Cases and controls were subdivided into rare variant carriers and non-carriers. Risk for ALS was significantly associated with PRS and rare variants independently, but the interaction was not significant. ALS PRS affected risk only in those not carrying a rare variant, suggesting that rare variants in ALS genes are generally sufficient for disease risk. Rather than modifying the penetrance of rare variants, ALS PRS is most informa...
ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a p... more ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious “cytokine storm. ”It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection.MethodsA 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically.ResultsFavorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8.DiscussionAs COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of A...
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient regist... more We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2001
ABSTRACT: Background: The aim of the present study was to identify the mutations in the connexin ... more ABSTRACT: Background: The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX). Methods: Molecular analysis was performed by nonisotopic single strand conformation polymorphism (SSCP) analysis and sequencing. Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium. Results: In one family, the mutation Arg142Trp was located in the transmembrane domain III whereas, in four other families we identified a novel mutation (Ser26Trp) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demy...
GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD)... more GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD) and tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia B. Recently, GCH1 mutations have also been reported in five patients with hereditary spastic paraplegia (HSP). In this study, a total of 400 HSP patients (291 families) from different centers across Canada were analyzed by whole exome sequencing (WES). Three patients with GCH1 variants were identified: monozygotic twins with a p.(Ser77_Leu82del) variant, and a patient with a p.(Val205Glu) variant. Both variants were predicted to be likely pathogenic. The three patients presented with childhood-onset spasticity in the lower limbs, hyperreflexia and abnormal plantar responses. Only one of the patients had diurnal fluctuations, and none had parkinsonism or dystonia. Phenotypic differences between the monozygotic twins were observed, and they responded well to levodopa treatment. Pathway enrichment analysis suggested that GCH1 sh...
BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlie... more BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.ObjectivesWe aimed to examine the association between heterozygous PRKN variants, including single nucleotide variants and copy-number variations, and PD.MethodsWe fully sequenced PRKN in 2,809 PD patients and 3,629 healthy controls, including 1,965 late onset (63.97±7.79 years, 63% men) and 553 early onset PD patients (43.33±6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. Copy-number variations were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single nucleotide variants and copy-number variations in PRKN are associated with PD risk and on...
The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highli... more The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highlights the role of the lysosome in Parkinson’s disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson’s disease have revealed multiple associated loci, including theGALClocus on chromosome 14.GALCencodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whetherGALCis the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.We first aimed to examine whether variants in theGALClocus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson’s Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson’s disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of common...
The genetic etiology of ALS includes few rare, large-effect variants and potentially many common,... more The genetic etiology of ALS includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. 335 ALS cases and 356 controls from Quebec, Canada were concurrently tested by SNP-chip genotyping and targeted sequencing of known ALS genes. ALS GWAS summary statistics were used to estimate an ALS PRS. Cases and controls were subdivided into rare variant carriers and non-carriers. Risk for ALS was significantly associated with PRS and rare variants independently, but the interaction was not significant. ALS PRS affected risk only in those not carrying a rare variant, suggesting that rare variants in ALS genes are generally sufficient for disease risk. Rather than modifying the penetrance of rare variants, ALS PRS is most informa...
ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a p... more ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious “cytokine storm. ”It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection.MethodsA 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically.ResultsFavorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8.DiscussionAs COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of A...
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient regist... more We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.
GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD)... more GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD) and tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia B. Recently, GCH1 mutations have also been reported in five patients with hereditary spastic paraplegia (HSP). In this study, a total of 400 HSP patients (291 families) from different centers across Canada were analyzed by whole exome sequencing (WES). Three patients with GCH1 variants were identified: monozygotic twins with a p.(Ser77_Leu82del) variant, and a patient with a p.(Val205Glu) variant. Both variants were predicted to be likely pathogenic. The three patients presented with childhood-onset spasticity in the lower limbs, hyperreflexia and abnormal plantar responses. Only one of the patients had diurnal fluctuations, and none had parkinsonism or dystonia. Phenotypic differences between the monozygotic twins were observed, and they responded well to levodopa treatment. Pathway enrichment analysis suggested that GCH1 sh...
BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlie... more BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.ObjectivesWe aimed to examine the association between heterozygous PRKN variants, including single nucleotide variants and copy-number variations, and PD.MethodsWe fully sequenced PRKN in 2,809 PD patients and 3,629 healthy controls, including 1,965 late onset (63.97±7.79 years, 63% men) and 553 early onset PD patients (43.33±6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. Copy-number variations were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single nucleotide variants and copy-number variations in PRKN are associated with PD risk and on...
The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highli... more The association between glucocerebrosidase (GCase), encoded byGBA, and Parkinson’s disease highlights the role of the lysosome in Parkinson’s disease pathogenesis. Genome-wide association studies (GWAS) in Parkinson’s disease have revealed multiple associated loci, including theGALClocus on chromosome 14.GALCencodes the lysosomal enzyme galactosylceramidase (GalCase), which plays a pivotal role in the glycosphingolipid metabolism pathway. It is still unclear whetherGALCis the gene driving the association in the chromosome 14 locus, and if so, by which mechanism.We first aimed to examine whether variants in theGALClocus and across the genome are associated with GalCase activity. We performed a GWAS in two independent cohorts from a)Columbia University and b)the Parkinson’s Progression Markers Initiative study, followed by a meta-analysis with a total of 976 Parkinson’s disease patients and 478 controls with available data on GalCase activity. We further analyzed the effects of common...
The genetic etiology of ALS includes few rare, large-effect variants and potentially many common,... more The genetic etiology of ALS includes few rare, large-effect variants and potentially many common, small-effect variants per case. The genetic risk liability for ALS might require a threshold comprised of a certain amount of variants. Here, we tested the degree to which risk for ALS was affected by rare variants in ALS genes, polygenic risk score, or both. 335 ALS cases and 356 controls from Quebec, Canada were concurrently tested by SNP-chip genotyping and targeted sequencing of known ALS genes. ALS GWAS summary statistics were used to estimate an ALS PRS. Cases and controls were subdivided into rare variant carriers and non-carriers. Risk for ALS was significantly associated with PRS and rare variants independently, but the interaction was not significant. ALS PRS affected risk only in those not carrying a rare variant, suggesting that rare variants in ALS genes are generally sufficient for disease risk. Rather than modifying the penetrance of rare variants, ALS PRS is most informa...
ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a p... more ObjectivesAcute necrotizing encephalopathy (ANE) is a rare neurological disorder arising from a para- or post-infectious “cytokine storm. ”It has recently been reported in association with coronavirus disease 2019 (COVID-19) infection.MethodsA 56-year-old male with a diagnosis of ANE 48 h following the first dose of ChAdOx1 nCoV-19 vaccination was investigated. Cytokine analyses on serum and cerebrospinal fluid (CSF) were performed. The patient was treated with high-dose corticosteroids and followed clinically and radiologically.ResultsFavorable clinical and radiological outcomes were noted. There was an upregulation in serum levels of CXCL5, CXCL1, Il-8, IL-15, CCL2, TGF-B, and EGF, and up-regulation in CSF levels of CXCL5, IL-2, IL-3, and IL-8.DiscussionAs COVID-19 infection has been previously reported as a possible rare cause of ANE, we speculate on an aberrant immune response mechanism that was brought about by the vaccine. To increase our understanding of the pathogenesis of A...
We report the recruitment activities and outcomes of a multi-disease neuromuscular patient regist... more We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 2001
ABSTRACT: Background: The aim of the present study was to identify the mutations in the connexin ... more ABSTRACT: Background: The aim of the present study was to identify the mutations in the connexin 32 gene in French-Canadian families with X-linked Charcot-Marie-Tooth disease (CMTX). Methods: Molecular analysis was performed by nonisotopic single strand conformation polymorphism (SSCP) analysis and sequencing. Clinical evaluation was carried out according to the scale defined by the European Hereditary Motor and Sensory Neuropathy Consortium. Results: In one family, the mutation Arg142Trp was located in the transmembrane domain III whereas, in four other families we identified a novel mutation (Ser26Trp) located in the transmembrane domain I of the connexin 32 gene. Haplotype analysis revealed that these four families are related and suggests a founder mutation. Sixteen patients from these four families were studied. As expected, all the affected males were more clinically affected than the females and all affected patients exhibited some electrophysiological characteristics of demy...
GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD)... more GCH1 mutations have been associated with dopa-responsive dystonia (DRD), Parkinson’s disease (PD) and tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia B. Recently, GCH1 mutations have also been reported in five patients with hereditary spastic paraplegia (HSP). In this study, a total of 400 HSP patients (291 families) from different centers across Canada were analyzed by whole exome sequencing (WES). Three patients with GCH1 variants were identified: monozygotic twins with a p.(Ser77_Leu82del) variant, and a patient with a p.(Val205Glu) variant. Both variants were predicted to be likely pathogenic. The three patients presented with childhood-onset spasticity in the lower limbs, hyperreflexia and abnormal plantar responses. Only one of the patients had diurnal fluctuations, and none had parkinsonism or dystonia. Phenotypic differences between the monozygotic twins were observed, and they responded well to levodopa treatment. Pathway enrichment analysis suggested that GCH1 sh...
BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlie... more BackgroundBiallelic PRKN mutation carriers with Parkinson’s disease (PD) typically have an earlier disease onset, slow disease progression and, often, different neuropathology compared to sporadic PD patients. However, the role of heterozygous PRKN variants in the risk of PD is controversial.ObjectivesWe aimed to examine the association between heterozygous PRKN variants, including single nucleotide variants and copy-number variations, and PD.MethodsWe fully sequenced PRKN in 2,809 PD patients and 3,629 healthy controls, including 1,965 late onset (63.97±7.79 years, 63% men) and 553 early onset PD patients (43.33±6.59 years, 68% men). PRKN was sequenced using targeted next-generation sequencing with molecular inversion probes. Copy-number variations were identified using a combination of multiplex ligation-dependent probe amplification and ExomeDepth. To examine whether rare heterozygous single nucleotide variants and copy-number variations in PRKN are associated with PD risk and on...
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