A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease

Bademci, Güney; Edwards, Todd L.; Torres, Audálio Rebelo; Scott, William K.; Züchner, Stephan; Martin, Eden R.; Vance, Jeffery M.; Wang, Liyong

doi:10.1002/humu.21351

Cited by 29 publications

(31 citation statements)

References 13 publications

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“…Previously reported 4 large genomic deletions involving GJB6 [25–27] were screened via quantitative PCR. CNV analysis for the genomic region of the GJB6 gene was performed with a TaqMan predesigned probe (Hs03843749, Chr13:20961484 on NCBI build 37) by using a previously described protocol [28]. For the Sanger sequencing, PCR reactions included 25 μg of genomic DNA with Taq DNA polymerase (Roche).…”

Section: Materials and Methodologymentioning

confidence: 99%

Common genes for non-syndromic deafness are uncommon in sub-Saharan Africa: A report from Nigeria

Lasisi

Bademci

Foster

et al. 2014

International Journal of Pediatric Otorhinolaryngology

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INTRODUCTION Little is known about the molecular epidemiology of deafness in sub-Saharan Africa (SSA). Even in Nigeria, the most populous African nation, no genetic studies of deafness have been conducted. This pioneering work aims at investigating the frequencies of gene mutations relatively common in other parts of the world (i.e. those in GJB2, GJB6, and mitochondrial DNA) among subjects from Nigeria with hearing loss (HL) with no evidence of acquired pathology or syndromic findings. In addition, we review the literature on the genetics of deafness in SSA. METHOD We evaluated 81 unrelated deaf probands from the Yoruba tribe residing in Ibadan, a suburban city in Nigeria, for the etiology of their deafness. Subjects underwent genetic testing if their history was negative for an environmental cause and physical examination did not find evidence of a syndrome. Both exons of GJB2 and mitochondrial DNA flanking the 1555A>G mutation were PCR-amplified followed by Sanger sequencing. GJB6 deletions were screened via quantitative PCR. RESULT We identified 44 probands who had nonsyndromic deafness with no environmental cause. The age at study time ranged between 8 months and 45 years (mean=24 years) and age at onset was congenital or prelingual (G mutations were not found among this initial cohort of the deaf in Nigeria. This makes imperative the search for other genes in the etiology of HL in this population.

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Section: Materials and Methodologymentioning

confidence: 99%

Common genes for non-syndromic deafness are uncommon in sub-Saharan Africa: A report from Nigeria

Lasisi

Bademci

Foster

et al. 2014

International Journal of Pediatric Otorhinolaryngology

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“…Thanks to the rapid advancement of biotechnologies, scientists are now able to scan entirely the human genome, producing high-quality ultradense genotypes and fast localization of genomic deletions and duplications. However, their applications in PD field are still not numerous, and only a few studies have investigated the overall contribution of global CNVs on PD etiology (Pankratz et al 2011; Simon-Sanchez et al 2008; Liu et al 2013; Pamphlett et al 2012; Bademci et al 2010). …”

Section: High-throughput Whole-genome Studies To Map Cnvs In Pdmentioning

confidence: 99%

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

et al. 2016

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Parkinson’s disease (PD), the second most common progressive neurodegenerative disorder of aging, was long believed to be a non-genetic sporadic origin syndrome. The proof that several genetic loci are responsible for rare Mendelian forms has represented a revolutionary breakthrough, enabling to reveal molecular mechanisms underlying this debilitating still incurable condition. While single nucleotide polymorphisms (SNPs) and small indels constitute the most commonly investigated DNA variations accounting for only a limited number of PD cases, larger genomic molecular rearrangements have emerged as significant PD-causing mutations, including submicroscopic Copy Number Variations (CNVs). CNVs constitute a prevalent source of genomic variations and substantially participate in each individual’s genomic makeup and phenotypic outcome. However, the majority of genetic studies have focused their attention on single candidate-gene mutations or on common variants reaching a significant statistical level of acceptance. This gene-centric approach is insufficient to uncover the genetic background of polygenic multifactorial disorders like PD, and potentially masks rare individual CNVs that all together might contribute to disease development or progression. In this review, we will discuss literature and bioinformatic data describing the involvement of CNVs on PD pathobiology. We will analyze the most frequent copy number changes in familiar PD genes and provide a “systems biology” overview of rare individual rearrangements that could functionally act on commonly deregulated molecular pathways. Assessing the global genome-wide burden of CNVs in PD patients may reveal new disease-related molecular mechanisms, and open the window to a new possible genetic scenario in the unsolved PD puzzle.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-016-1749-4) contains supplementary material, which is available to authorized users.

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“…The genome-wide association study found a deletion in tyrosine hydroxylase, enzyme involved in dopamine synthesis, in one adult PD [214] whereas missense mutations in tyrosine hydroxylase gene were already involved in infantile parkinsonism [215].…”

Section: Tyrosine Hydroxylasementioning

confidence: 99%

Mechanisms Implicated in Parkinson Disease from Genetic Perspective

Popescu¹

2016

Med Clin Rev

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Parkinson's disease (PD) etiology is based upon interactions between genetic susceptibility and the environmental exposure. Multiple environmental factors inducing oxidative stress, mitochondrial damage, impairment of the neuroprotective and autophagic mechanisms are responsible for dopaminergic neurons death. Defining the contributions of genetic and environmental factors, may have important implications for understanding the pathogenesis of PD. The linkage analysis in Mendelian forms of PD especially in multiplex highly penetrant families is essential to elucidate biological mechanisms for PD susceptibility. Concerning the monogenic forms of PD were found mutations in 7 genes of AD transmission (SNCA, LRRK2, GIGYF2, VPS35, EIF4G1, HTRA2, TMEM230) and even more in those of AR transmission. This review aims to give an overview of the existing evidence of multiples molecular pathways involving cytoplasmic organelles' function, neurodevelopmental mechanisms, synaptic vesicles endocytosis and trafficking, maintaining the integrity of the cytoskeleton and axonal transport in neurons. Understanding the molecular mechanisms following the identification of genes mutations and low-penetrance susceptibility alleles in familial and sporadic PD patients by genotyping technology and functional studies represent an essential step for the development of adequate biomarkers and potent therapies.

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A rare novel deletion of the tyrosine hydroxylase gene in Parkinson disease

Cited by 29 publications

References 13 publications

Common genes for non-syndromic deafness are uncommon in sub-Saharan Africa: A report from Nigeria

Common genes for non-syndromic deafness are uncommon in sub-Saharan Africa: A report from Nigeria

Copy number variability in Parkinson’s disease: assembling the puzzle through a systems biology approach

Mechanisms Implicated in Parkinson Disease from Genetic Perspective

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