: A Customized aCGH for the Analysis of Copy Number Variations in Neurological Disorders.

Background: Neurological disorders are a highly heterogeneous group of pathological conditions that affect both the peripheral and the central nervous system. These pathologies are characterized by a complex and multifactorial etiology involving numerous environmental agents and genetic susceptibility factors. For this reason, the investigation of their pathogenetic basis by means of traditional methodological approaches is rather arduous.

Italian folk plant-based remedies to heal headache (XIX-XX century).

Background: Headache has been recognized since antiquity. From the late nineteenth to the early to mid-twentieth century, Italian folk remedies to treat headache were documented in a vast corpus of literature sources.

Aim: The purpose of this paper is to bring to light the plant-based treatments utilized by Italian folk medicine to heal headache in an attempt to discuss these remedies from a modern pharmacological point of view.

Copy Number Variants in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating disease mainly afflicting elderly people, characterized by decreased cognition, loss of memory, and eventually death. Although risk and deterministic genes are known, major genetics research programs are underway to gain further insights into the inheritance of AD. In the last years, in particular, new developments in genome-wide scanning methodologies have enabled the association of a number of previously uncharacterized copy number variants (CNVs, gain or loss of DNA) in AD.

Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson's disease - a multicenter study.

Background: The transcription factor Nrf2, encoded by the NFE2L2 gene, is an important regulator of the cellular protection against oxidative stress. Parkinson's disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of NFE2L2 haplotypes with risk and age at onset of idiopathic Parkinson's disease in a Swedish discovery material and a Polish replication material.

Potential involvement of GRIN2B encoding the NMDA receptor subunit NR2B in the spectrum of Alzheimer's disease.

Increasing evidence links dysregulation of NR2B-containing N-methyl-D-aspartate receptor remodelling and trafficking to Alzheimer's disease (AD). This theme offers the possibility that the GRIN2B gene, encoding this selective NR2B subunit, represents a potential molecular modulating factor for this disease. Based on this hypothesis, we carried out a mutation scanning of exons and flanking regions of GRIN2B in a well-characterized cohort of AD patients, recruited from Southern Italy.

A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies.

Importance: While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders.

Objective: To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers.

Spinocerebellar ataxia type 7: report of a new Italian family.

Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by degeneration of the cerebellum, brainstem and retina. We herein describe a family from southern Italy whose proband was a 49-year-old man presenting with ataxia with progressive gait disturbances, clumsiness and visual impairment. A molecular analysis identified 38 cytosine-adenine-guanine (CAG) repeat expansions within the SCA7 gene.

Mutation analysis of the PINK1 gene in Southern Italian patients with early- and late-onset parkinsonism.

Mutations in the PINK1 gene represent the second most frequent cause of early-onset Parkinson's disease (EOPD). One or two mutated alleles were also reported in some sporadic or familial patients suffering from late-onset Parkinson's disease (LOPD). We aimed at assessing the frequency of mutations in this gene in our population.

Association study between four polymorphisms in the HFE, TF and TFR genes and Parkinson's disease in southern Italy.

Iron overload may lead to neurodegenerative disorders such as Parkinson's disease (PD) and alterations of iron-related genes might be involved in the pathogenesis of this disease. The gene of haemochromatosis (HFE) encodes the HFE protein which interacts with the transferrin receptor (TFR), lowering its affinity for iron-bound transferrin (TF). We examined four known polymorphisms, C282Y and H63D in the HFE gene, G258S in the TF gene and S82G in the TFR gene, in 181 sporadic PD patients and 180 controls from Southern Italy to investigate their possible role in susceptibility to PD.

Lack of association between G-protein coupled receptor kinase 5 gene and Parkinson's disease.

The major component of Lewy Bodies (LB), the pathological hallmark of Parkinson's disease (PD) is α-synuclein, most prominently phosphorylated at serine 129. G-protein coupled receptor kinase 5 (GRK5) has been reported to phosphorylate α-synuclein in vitro, enhancing the α-synuclein toxicity to dopaminergic neurons in Drosophila model. Moreover, GRK5 was found in LBs from brain of PD patients.

Single nucleotide polymorphism in the MMP-9 gene is associated with susceptibility to develop multiple sclerosis in an Italian case-control study.

To investigate the role of the matrix metalloproteinase-9 gene (MMP-9) in multiple sclerosis (MS), we analyzed the functional -1562C/T and -90 (CA)(n) repeat polymorphisms in 243 Italian patients with MS and 173 healthy controls. A significant increase of the -1562T allele carriers was found in patients with MS compared to controls. Moreover, haplotype analysis showed that the haplotype formed by the -1562T allele and the L allele ((CA)( View Article and Find Full Text PDF

Myocardial (123)I-MIBG scintigraphy for differentiation of Lewy bodies disease from FTD.

Clinical distinction between Lewy bodies disease (LBD) and frontotemporal dementia (FTD) is sometimes difficult. Nigrostriatal dopaminergic degeneration occurs in both LBD and FTD, limiting helpfulness of DAT imaging to differentiate these forms of dementia. Several studies have emphasized the usefulness of myocardial scintigraphy with (123)Metaiodobenzylguanidine ((123)I-MIGB) in assessing the sympathetic nerve terminals in LBD demonstrating that cardiac (123)I-MIGB uptake is decreased in patients with this disease.

Compound heterozygosity in DJ-1 gene non-coding portion related to parkinsonism.

In this study we analysed the DJ-1 gene in 40 sporadic patients with early onset Parkinson's disease and 100 appropriate controls, originated from southern Italy. We identified a single patient with age at onset of 38 years carrying two previously undescribed heterozygous mutations, both located in non-coding regions. The first mutation was a nucleotide change in the promoter region of the gene (g.

Glucocerebrosidase gene mutations are associated with Parkinson's disease in southern Italy.

Recent studies have reported an association between the glucocerebrosidase (GBA) gene and Parkinson's disease (PD). To elucidate the role of this gene in our population, we screened 395 PD patients and 483 controls from southern Italy for the N370S and the L444P mutations. We found 11 patients (2.

Further evidence of genetic heterogeneity in families with autosomal dominant nocturnal frontal lobe epilepsy.

Purpose: Mutations in the genes encoding the alfa(2), alfa(4) and beta(2) subunits of the neuronal nicotinic acetylcholine receptor (nAChR) play a causative role in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Moreover, variations in the promoter of the corticotropic-releasing hormone gene (CRH) were also associated with ADNFLE. Here, we investigated whether nine brain-expressed genes (CHRNA2, CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4), encoding distinct nAChR subunits, and CRH are associated with the disease in three distinct ADNFLE families from Southern Italy.

Genetic heterogeneity in patients with pantothenate kinase-associated neurodegeneration and classic magnetic resonance imaging eye-of-the-tiger pattern.

We performed a detailed molecular study in two unrelated families with pantothenate kinase-associated neurodegeneration (PKAN) and the specific magnetic resonance imaging (MRI) eye-of-the-tiger pattern. In the first family with classic PKAN, linkage analysis using polymorphic markers from the PANK2 region ruled out linkage with this locus, and no mutation of the PANK2 gene was found. In the second family with atypical PKAN, we identified a novel homozygous C-to-T transition at nucleotide 1069 of the PANK2 gene, which resulted in an arginine to tryptophane substitution at codon 357.

Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study.

Background: Several factors, both clinical and genetic, may account for the risk of developing levodopa-induced peak-dose dyskinesias (PDD) in patients with Parkinson disease, but it is unclear how these factors interact for modulating the individual susceptibility for PDD.

Objective: To examine clinical and genetic risk factors for determining individual susceptibility of PDD in patients with Parkinson disease.

Design: Cohort study.

Chronic bilateral subthalamic deep brain stimulation in a patient with homozygous deletion in the parkin gene.

Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness.