The co‐occurrence of early onset Parkinson disease and 22q11.2 deletion syndrome

Zaleski, Christina; Bassett, Anne S.; Tam, Karen; Shugar, Andrea; Chow, Eva W.C.; McPherson, Elizabeth

doi:10.1002/ajmg.a.32650

Cited by 52 publications

(54 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are some initial indications that early onset Parkinson's disease may be a late manifestation of the syndrome (Booij et al 2010;Zaleski et al 2009). Although further studies are needed to investigate this association, it may be that, as for other syndromes, aberrant neurodevelopment in 22q11.2DS may set the stage for increased risk of neurodegenerative conditions.…”

Section: Cognitive and Behavioural Phenotype Of 22q112 Dsmentioning

confidence: 99%

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

2011

View full text Add to dashboard Cite

Abstract22q11.2 Deletion syndrome has become an important model for understanding the pathophysiology of neurodevelopmental conditions, particularly schizophrenia which develops in about 20-25% of individuals with a chromosome 22q11.2 microdeletion. From the initial discovery of the syndrome, associated developmental delays made it clear that changes in brain development were a key part of the expression. Once patients were followed through childhood into adult years, further neurobehavioural phenotypes became apparent, including a changing cognitive profile, anxiety disorders and seizure diathesis. The variability of expression is as wide as for the myriad physical features associated with the syndrome, with the addition of evolving phenotype over the developmental trajectory. Notably, variability appears unrelated to length of the associated deletion. Several mouse models of the deletion have been engineered and are beginning to reveal potential molecular mechanisms for the cognitive and behavioural phenotypes observable in animals. Both animal and human studies hold great promise for further discoveries relevant to neurodevelopment and associated cognitive, behavioural and psychiatric disorders.

show abstract

Section: Cognitive and Behavioural Phenotype Of 22q112 Dsmentioning

confidence: 99%

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

2011

View full text Add to dashboard Cite

show abstract

“…Six cases of PD associated with 22q11.2DS have so far been reported in the literature (3)(4)(5). The clinical features of these previously reported cases and our own case are summarized in the Table. In all cases, motor symptoms began before the fifth decade of life and responded well to levodopa therapy.…”

Section: Discussionmentioning

confidence: 99%

Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome

et al. 2016

View full text Add to dashboard Cite

We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of 123 I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease.

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

The co‐occurrence of early onset Parkinson disease and 22q11.2 deletion syndrome

Cited by 52 publications

References 21 publications

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

Cognitive, Behavioural and Psychiatric Phenotype in 22q11.2 Deletion Syndrome

Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome

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

Contact Info

Product

Resources

About