Exome-wide rare variant analysis in familial essential tremor.

Introduction: Essential tremor (ET) is one of the most common movement disorders. Despite its high prevalence and heritability, its genetic etiology remains elusive with only a few susceptibility genes identified and poorly replicated. Our aim was to find novel candidate genes involved in ET predisposition through whole exome sequencing.

Pooled-DNA target sequencing of Parkinson genes reveals novel phenotypic associations in Spanish population.

Eighteen loci and several susceptibility genes have been related to Parkinson's disease (PD). However, most studies focus on single genes in small PD series. Our aim was to establish the genetic background of a large Spanish PD sample.

Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.

Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families.

TREM2 R47H variant and risk of essential tremor: a cross-sectional international multicenter study.

Introduction: Essential tremor (ET) is the most frequent movement disorder in adults. Its pathophysiology is not clearly understood, however there is growing evidence showing common etiologic factors with other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases (AD, PD). Recently, a rare p.

Nigrostriatal dopaminergic function in subjects with isolated action tremor.

Background: Isolated action tremor (IAT) is the hallmark clinical feature of essential tremor (ET), but it may also be a prominent feature of some individuals with Parkinson's disease (PD) suggesting a pathogenic relationship between these two disorders.

Objectives: We investigated the integrity of the striatal presynaptic dopaminergic system in subjects presenting IAT to improve the diagnostic accuracy and to explore any putative relationships between ET and PD.

Methods: The striatal dopaminergic system was examined by means of dopamine transporter imaging using (123)I-(fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane ([123I]-FP-CIT) single-photon emission tomography (DAT-SPECT) in a clinical series of individuals with IAT, excluding those with associated resting tremor and bradykinesia.

Genetic variation in APOE cluster region and Alzheimer's disease risk.

We report the fine mapping/sequencing results of promoter and regulatory regions of APOE cluster genes (APOE, APOC1, APOC4, APOC2, and TOMM40) in Alzheimer's disease (AD) risk as well as in the progression from mild cognitive impairment (MCI) to AD. Long-range sequencing in 29 MCI subjects who progressed to dementia revealed 7 novel variants. Two potentially relevant novel variants and 34 single nucleotide polymorphisms (SNPs) were genotyped in a large sample of AD, MCI, and control subjects (n = 1453).

LINGO1 gene analysis in Parkinson's disease phenotypes.

Background: Parkinson's disease (PD) and essential tremor (ET) may share some etiopathogenic factors. A genome-wide association study has shown that LINGO1 gene variants are associated with increased risk of ET. We hypothesized that LINGO1 variants could increase susceptibility to PD.

Rasagiline improves freezing in a patient with primary progressive freezing gait.

We herein report the case of a 84-year-old man with a 4-year history of freezing of gait (FOG) consistent with the diagnosis of primary progressive freezing gait. Single photon emission tomography (SPECT) with a radiolabeled ligand of the dopamine transporter (DAT-SPECT) showed integrity of striatal dopaminergic terminals, whereas brain perfusion SPECT disclosed multiple areas of decreased perfusion in frontal and parietal lobes, as well as in the subcortical gray nuclei of both sides. Treatment with the new irreversible monoamine oxidase B inhibitor rasagiline at standard doses resulted in a rapid, dramatic, and sustained improvement of the frequency and duration of FOG episodes.

Molecular genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1 gene.

The deafness-dystonia syndrome (DDS) or Mohr-Tranebjaerg syndrome (MTS, MIM 304700) is a rare X-linked recessive neurological disorder resulting from loss-of-function mutations in the nuclear DDP1/TIMM8A gene, involved in the transport and sorting of proteins to the mitochondrial inner membrane. A Mohr-Tranebjaerg patient and his mother were subjected to clinical and molecular studies. Screening of mutations were performed in TIMM8A, TIMM13, and other mitochondrial protein transport genes by conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing of tissue samples from the patient.

A TAP2 genotype associated with Alzheimer's disease in APOE4 carriers.

Sporadic Alzheimer's disease (AD) appears to be the consequence of the interaction between combinations of genes and environmental factors. Binding with the transporter associated with antigen processing (TAP) is thought to be the main way in which herpes simplex virus type 1 (HSV-1) evades immune surveillance. Several TAP gene polymorphisms were examined and a TAP2 SNP (rs241448) associated with AD found in two independent case-control samples, especially in carriers of the APOE4 allele.

Polymorphism in genes involved in adrenergic signaling associated with Alzheimer's.

To investigate the potential involvement of adrenergic signaling in Alzheimer's disease (AD) pathogenesis, we performed genetic and functional studies of genes initiating the cascade. We chose two functional single-nucleotide polymorphisms (SNPs) in the beta1-adrenergic receptor (ADRB1) and the G protein beta3 subunit (GNB3) genes, respectively, and analyzed their allelic frequencies in a case-control sample of AD. We found that the GNB3 T allele produces a significant risk for AD in individuals homozygous for the ADRB1 C allele, suggesting that the combined effect of both polymorphisms influences AD susceptibility.