Co‐occurrence of early‐onset Parkinson disease and 22q11.2 deletion syndrome: Potential role for dopamine transporter imaging

Booij, Jan; Amelsvoort, Thérèse van; Boot, Erik

doi:10.1002/ajmg.a.33665

Cited by 46 publications

(63 citation statements)

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“…Additionally, Cytochrome P450 (CYP), and in particular CYP2D6, which has polymorphic expression, and which is expressed in neurons and in the gut has a different expression in PD patients, where it has been found preponderantly as CYP2D6*4 allele [267] CYP2D6 acts as a 25-hydroxylase, which is able to convert vitamin D3 into 25OHD, being the key enzyme to determine a deficiency of vitamin D. In mouse MPTP treated model (inducing PD phenotype), Singh et al [268] reported the strong expression of the animal ortholog of CYP2D6, CYP2D22. Very interestingly, CYP2D loci are located on chromosome 22 where many genes related to PD are segregated [269][270][271]. It seems surprising that deletion of chromosome 22q11 was reported to be associated to PD [271] but also with a reduced serum calcium and a reduced level of vitamin D [272].…”

Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

“…Very interestingly, CYP2D loci are located on chromosome 22 where many genes related to PD are segregated [269][270][271]. It seems surprising that deletion of chromosome 22q11 was reported to be associated to PD [271] but also with a reduced serum calcium and a reduced level of vitamin D [272]. According with cytoprotection, there are three more links, between vitamin D and PD.…”

Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

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Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Moretti

Morelli

Caruso

2018

Preprint

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It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA).Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration.Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions.We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation. Peer-reviewed version available at Int. J. Mol. Sci. 2018, 19, 2245 doi:10.3390/ijms19082245 3 SEARCH STRATEGY AND SELECTION CRITERIAWe searched MEDLINE using the search terms: "vitamin D central nervous system" , both "vitamin D" and "central nervous system"; "vitamin D immune system/response", both "vitamin D" and "immune system" or "immune response"; "vitamin D multiple sclerosis risk", both "vitamin D" and "multiple sclerosis risk"; "vitamin D multiple sclerosis relapse", both "vitamin D" and "multiple sclerosis relapse"; "vitamin D multiple sclerosis magnetic resonance imaging", both "vitamin D" and "multiple sclerosis magnetic resonance imaging"; "vitamin D multiple sclerosis disability", both "vitamin D" and "multiple sclerosis disability"; "vitamin D supplementation/therapy/treatment multiple sclerosis", both "vitamin D supplementation" or "vitamin D therapy" or "vitamin D treatment" and "multiple sclerosis"; "vascular dementia", both as -vascular-and -dementia-, "subcortical vascular dementia", both assubcortical-and -dementia-, "Alzheimer's disease", "pathogenesis neurodegeneration" "amyloid", "cholinergic afferents", "arteriolosclerosis", "cerebral flow regulation", "stroke". Publications were selected mostly form the past 20years, but did not exclude frequently referenced and highly regarded older publications. . Congress abstracts and isolated case reports were not considered. We searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles and book chapters are cited to provide with ...

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Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

Section: Vitamin D Deficiency and Neurodegenerative Diseasesmentioning

confidence: 99%

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Moretti

Morelli

Caruso

2018

Preprint

View full text Add to dashboard Cite

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“…Patients affected by the two conditions may carry a single, common genetic defect, as previously suggested [6,9], leading to the consideration of PD as part of the phenotypic spectrum of 22q11.2DS, as suggested by Butcher et al [10] and more recently by Mok et al…”

Section: R E V I S E D M a N U S C R I P Tmentioning

confidence: 96%

“…The 22q11.2DS, usually diagnosed in children, is exceptionally diagnosed in adults where it usually manifests as a long history of psychiatric disorders such as schizophrenia [4,5]. Some authors first reported co-occurrences of early onset Parkinson disease (EOPD) and 22q11.2DS [4,[6][7][8] and searched for any molecular links [6,9]. Based on a few reports, an increased risk of EOPD has recently been suggested in 22q11.2DS [10] and confirmed in a recent article [11] where the authors reported the risk of EOPD conferred by deletions at 22q11.2 was about 20-times increased.…”

Section: Introductionmentioning

confidence: 99%

Parkinson's disease associated with 22q11.2 deletion: Clinical characteristics and response to treatment

et al. 2017

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Background. 22q11.2 microdeletions (22q11.2-del) increase the risk of Parkinson's disease (PD) but the characteristics of PD associated to 22q11.2-del have not been specifically explored.Objective. To assess clinical and treatment-response characteristics, and to describe features that may lead a neurologist to investigate this comorbidity.Methods. We report and describe 9 PD patients (8 men, 1 woman) followed in 7 centers of the French PD Expert Network (Ns-Park) also presenting the 22q11.2-del.Results. PD diagnosis was made prior to 22q11.2-del diagnosis in 7 cases, the main characteristics are an early onset (32-48 y), a good initial DOPA-sensitivity but with a severe course characterized by severe and early-onset levodopa-induced motor complications and psychiatric manifestations. Three patients received deep-brain stimulation (DBS) with efficacy.Conclusions. Searching for 22q11.2-del in PD patients presenting suggestive features is relevant as the clinical presentation is close to idiopathic PD but with associated characteristics including a severe evolution. Results of DBS are similar to those reported in idiopathic PD.

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“…Several case reports of individuals with the hemizygous deletion of chromosome 22q11.2 and some clinical features of Parkinsonism have suggested that this genetic anomaly may also confer an increased risk of early-onset PD [113][114][115]. Some of these cases were reported to be treated with L-DOPA, while in other case, presynaptic dopamine imaging indicated degeneration of the nigrostriatal dopamine system [113][114][115]. To investigate the association between 22q11.2 deletions and PD, Butcher and colleagues [116] assessed the occurrence of a clinical diagnosis of PD in a wellcharacterized cohort of adults with 22qDS.…”

Section: The 22q112 Deletionmentioning

confidence: 99%

Genetics of Parkinson’s Disease: The Role of Copy Number Variations

Cognata¹,

D’Agata²,

Cavalcanti³

et al. 2016

Challenges in Parkinson's Disease

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Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, was long believed to be a non-genetic sporadic origin syndrome. The identification of distinct genetic loci responsible for rare Mendelian forms of PD has represented a revolutionary breakthrough, allowing to discover novel mechanisms underlying this debilitating still incurable condition. Along with single-nucleotide polymorphisms (SNPs), other kinds of DNA molecular defects have emerged as significant disease-causing mutations, including large chromosomic structural rearrangements and copy number variations (CNVs). Due to their size variability and to the different sensitivity and resolution of detection methodologies, CNVs constitute a particular challenge in genetic studies and the pathogenetic or susceptibility impact of specific CNVs on PD is currently under debate. In this chapter, we will review the current literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will discuss the recently highlighted role of PARK2 heterozygous CNVs, the possible common founder effects of PD gene rearrangements and the importance to map genetic breakpoints. We will also add a summary about the current available molecular methods and bioinformatics web resources to detect and interpret CNVs. Assessing the global genome-wide burden of large CNVs and elucidating the role of de novo rare structural variants on PD may reveal new candidate genes and consequently ameliorate diagnosis and counselling of mutations carriers.

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Co‐occurrence of early‐onset Parkinson disease and 22q11.2 deletion syndrome: Potential role for dopamine transporter imaging

Cited by 46 publications

References 4 publications

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Parkinson's disease associated with 22q11.2 deletion: Clinical characteristics and response to treatment

Genetics of Parkinson’s Disease: The Role of Copy Number Variations

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