Mutation Analysis Of The Pink1 Gene In 391 Patients With Parkinson Disease

Objectives: To determine the frequency, distribution, and clinical features of Parkinson disease (PD) with PINK1 mutations. Design: Retrospective clinical and genetic review. Setting: University hospital. Patients: We performed extensive mutation analyses of PINK1 in 414 PD patients negative for parkin mutations (mean [SD] age at onset, 42.8 [14.3] years), including 391 unrelated patients (190 patients with sporadic PD and 201 probands of patients with familial PD) from 13 countries. Results: We found 10 patients with PD from 9 families with PINK1 mutations and identified 7 novel mutations (2 homozygous mutations [p. D297MfsX22 and p. W437R] and 5 single heterozygous mutations [p. A78V, p. P196QfsX25, p. M342V, p. W437R, and p. N542S]). No compound heterozygous mutations were found. The frequency of homozygous mutations was 4.26% (2 of 47) in families with autosomal recessive PD and 0.53% (1 of 190) in patients with sporadic PD. The frequency of heterozygous mutations was 1.89% (2 of 106) in families with potential autosomal dominant PD and 1.05% (2 of 190) in patients with sporadic PD. The mean (SD) age at onset in patients with single heterozygous mutations (53.6 [11.1] years; range, 39-69 years) was higher than that in patients with homozygous mutations (34.0 [20.3] years; range, 10-55 years). Myocardial iodine-123 metaiodobenzylguanidine uptake was low in patients with heterozygous mutations but not in those with homozygous mutations. Conclusions: Our results suggest that homozygous PINK1 mutations tend to be diagnosed as the early-onset autosomal recessive form of PD. Single heterozygous mutations may contribute to the development of sporadic PD and also could be an additional genetic predisposition for developing familial PD. The reduced myocardial iodine-123 metaiodobenzylguanidine uptake observed in patients with single heterozygous PINK1 mutations is similar to that seen in patients with sporadic PD.WoSScopu

Mutation analysis of the PARKIN, PINK1, DJ1, and SNCA genes in Turkish early-onset Parkinson's patients and genotype-phenotype correlations

Objective: Variations in PARK genes (PRKN, PINK1, DJ-1, and SNCA) cause early-onset Parkinson's disease (EOPD) in different populations. In the current study, we aimed to evaluate the frequencies of variations in PARK genes and the effects of these variations on the phenotypes of Turkish EOPD patients. Methods: All coding regions and exon-intron boundaries of the PRKN, PINK1, DJ-1, and SNCA genes were screened by heteroduplex analysis followed by direct sequencing of the detected variants in 50 Turkish EOPD patients. These variants were evaluated using SIFT, PolyPhen, HSF, and LOVD web-based programs. Results: The frequency of EOPD-associated variations in the PRKN gene was 34%. Among these variations, p.A82E in exon 3 and p.Q409X in exon 11 was determined to be pathogenic. We also defined previously unknown cryptic variations, including c.872-35 G > A and c.872-28T > Gin exon 8 of PRKN and c.252 + 30 T > G and c.322 + 4 A > G in exons 4 and 5 of DJ1, respectively, that were associated with EOPD. Although no significant association was observed between the PARK gene mutations and clinical features (P > 0.05), the alterations were related to the clinical symptoms in each patient. Conclusion: An increasing number of studies report that PRKN, PINK), DJ1 and SNCA mutations are associated with early-onset Parkinson's disease; however, a limited number of studies have been conducted in Turkey. Additionally, our study is the first to evaluate the frequency of SNCA mutations in a Turkish population. The aim of this study was determine the frequency distributions of the PRKN, PINK1, DJ1, and SNCA gene mutations and to analyze the relationships between these genetic variations and the clinical phenotype of EOPD in Turkish patients

Apomorphine in the Treatment of Parkinson's Disease

Apomorphine is a dopamine agonist used in the treatment of some motor and non-motor complications during Parkinson's disease, which could be administered as an intermittent or continuous infusion. Although apomorphine treatment has been shown to be effective on motor fluctuations and dyskinesias, there is no sufficient consensus regarding the administration of apomorphine test or infusion, and the management of the treatment. In this review, our aim is to create a "treatment management guideline," which includes recommendations for the use of apomorphine in the clinical practice, and to discuss the problems encountered in both intermittent and continuous infusion applications, in the light of the literature

Epigenetic approach to early-onset Parkinson's disease: Low methylation status of SNCA and PARK2 promoter regions

Background and aim: The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD). Materials and methods: The promoter region methylation status of SNCA and PARK2 genes was evaluated by methylation specific-PCR (MSP) in 91 patients with EOPD and 52 healthy individuals. Results: The methylation of SNCA and PARK2 promoter regions were significantly lower in EOPD patients compared to the control group (P = 0.013 and P = 0.03, respectively). We also found that the methylation status of the SNCA might be associated with positive family history of PD (P = 0.042). Conclusion: Although it should be supported by further analysis, based on the results of the present study, the methylation status of SNCA and PARK2 genes might contribute to EOPD pathogenesis

Use of anti-Parkinson medication during pregnancy: a case series

Introduction Experience about the use and safety of anti-Parkinson (anti-PD) medication during pregnancy is scarce

Default Mode Network Connectivity Is Linked to Cognitive Functioning and Csf A Beta(1-42) Levels In Alzheimer'S Disease

Background: Changes in the default mode network (DMN) activity are early features of Alzheimer's disease (AD) and may be linked to AD-specific A beta pathology. Methods: Cognitive profiles; DMN connectivity alterations; and cerebrospinal fluid (CSF) amyloid beta (A beta)(1-42), total tau, phosphorylated tau 181, and alpha-synuclein levels were studied in 21 patients with AD and 10 controls. Results: DMN activity is altered in AD. Posterior cingulate cortex (PCC) functional connectivity with other parts of DMN was related to cognitive function scores. The reduction of connectivity of the dorsal PCC with the retrosplenial cortex on the right side was closely related to decreased CSF A beta(1-42) levels in patients with AD. Conclusions: The dorsal PCC and retrosplenial cortex may have special importance in the pathogenesis and cognitive findings of AD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Wo

Nöroloji Staj Notları

Nöroloji Staj NotlarıBu kitap, Dönem V Nöroloji Stajı boyunca öğrencilerin elinde temel bir rehber olmasını sağlamak amacıyla hazırlanmıştır. Hastaya, hikayesine ve bulgularına bir bilmece gibi yaklaşmak, lezyon “nerededir?” ve “nedir?” sorularının yanıtını aramak nörolojiyi zevkli kılan özelliklerdir. İyi bir hikaye almanın önemi hemen her bölümde vurgulanmıştır. Klinik nörolojinin temel ve güncel kavramlarını içermekle birlikte tüm bilgiyi 200 sayfalık bu kitapçığa sığdırmak mümkün değildir. Eksik konular için önerilen kaynaklar kitabın sonunda verilmiştir. Bu ikinci baskıda öğrencilerden ve öğretim üyelerinden gelen görüşler doğrultusunda düzeltmeler yapılmış, nöroanatomik kısa bilgiler ve güncel kavramlar eklenmiştir. Bilgiye ulaşmak için çok çeşitli kaynakların var olduğu bir dönemde, elde temel bir kitabın var olmasının, öğrencinin araştırmacı yönünü azaltmayacağını, aksine artıracağını umuyoruz

Epigenetic approach to early-onset Parkinson's disease: low methylation status of SNCA and PARK2 promoter regions

Background and aim: The effect of epigenetic modifications in the genes related to Parkinson's disease (PD) is still unclear. In the present study, we investigated methylation status of SNCA and PARK2 genes in patients with early-onset Parkinson's disease (EOPD)