Detection of copy number changes in genes associated with Parkinson's disease in Iranian patients

Darvish, Hossein; Movafagh, Abolfazl; Omrani, Mir Davood; Firouzabadi, Saghar Ghasemi; Azargashb, Eznollah; Jamshidi, Javad; Khaligh, Ali; Haghnejad, Leyla; Naeini, Nilofar Safavi; Talebi, Atefeh; Heidari-Rostami, Hamid Reza; Noorollahi-Moghaddam, Hamid; Karkheiran, Siamak; Shahidi, Gholam Ali; Paknejad, Seyed Mohammad Hassan; Ashrafian, Hossein; Abdi, Salman; Kayyal, Matin; Akbari, ME; Pedram, Negar; Emamalizadeh, Babak

doi:10.1016/j.neulet.2013.07.013

Cited by 32 publications

(25 citation statements)

References 12 publications

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“…PD families with members carrying four copies of SNCA gene have been detected in South Africa, Iran, Japan, Pakistan and Italy [35][36][37][38][39][40]: in general, triplication generates very high expression of mRNA and protein and influences the clinical manifestations of PD, causing severe forms of Parkinsonism similar to dementia with Lewy body. Duplications have been reported in more numerous families than triplications [33,38,[41][42][43][44][45][46][47][48][49][50][51]. In some of the patients with the same ethnic background (Japan), haplotype analysis revealed their derivation from common founders [43,44].…”

Section: Sncamentioning

confidence: 99%

“…Homozygous deletions involving different combination of exons 4-8 have been described in both familial and sporadic early-onset cases coming from Japan, Brazil, Sudan and Iran [38,[88][89][90][91]. Just in one of them, breakpoint analysis has been performed, revealing a complex rearrangement combining a large deletion and the insertion of a duplicated sequence from the neighbouring DDOST gene intron 2 [91].…”

Section: Pink1mentioning

confidence: 99%

“…As suggested by breakpoint analysis, this rearrangement may result from FoSTeS mechanism. Only one case of a sporadic patient carrying two different CNVs on PINK1 (compound heterozygous mutations) has been reported until now, consisting of exon 2 deletion in one allele and exons 2-4 deletion in the other one [38].…”

Section: Pink1mentioning

confidence: 99%

“…In one of the families, a 14 kb deletion involving the first five of seven exons in the DJ-1 gene has been identified [95]. Furthermore, three siblings of Iranian origins born from consanguineous parents and carriers of a homozygous deletion of exon 5 have been described [38].…”

Section: Dj1mentioning

confidence: 99%

“…To our knowledge, just one family from Iran with deletion of ATP13A2 has been reported [38]. Specifically, three affected siblings born from consanguineous parents have been described as carriers of a homozygous deletion of exon 2.…”

Section: Atp13a2mentioning

confidence: 99%

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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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Section: Sncamentioning

confidence: 99%

Section: Pink1mentioning

confidence: 99%

Section: Pink1mentioning

confidence: 99%

Section: Dj1mentioning

confidence: 99%

Section: Atp13a2mentioning

confidence: 99%

See 3 more Smart Citations

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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Genome‐Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

et al. 2020

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Background Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non‐European populations. In addition, the overall identification of copy number variants at a genome‐wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome‐wide burden of copy number variants in Latinos and its association with Parkinson's disease. Methods We used genome‐wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. Results Genome‐wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69–10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10−7). Conclusions We found that although overall genome‐wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early‐onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome‐wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society

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Genetics of Metal Disorders (Excluding NBIA)

Dušek

Záhoráková

2015

Movement Disorder Genetics

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Detection of copy number changes in genes associated with Parkinson's disease in Iranian patients

Cited by 32 publications

References 12 publications

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

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

Genome‐Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients

Genetics of Metal Disorders (Excluding NBIA)

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