Duplications Are Associated With Progressive Muscular Atrophy, but Not With Multifocal Motor Neuropathy and Primary Lateral Sclerosis.

Objective: To assess the association between copy number (CN) variation in the survival motor neuron () locus and multifocal motor neuropathy (MMN), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS) susceptibility and to determine the association of and CN with MMN, PMA, and PLS disease course.

Methods: In this monocenter study, we used multiplex ligation-dependent probe amplification to determine and CN in Dutch patients with MMN, PMA, and PLS and controls. We stratified clinical parameters for and CN.

Multiplex Ligation-Dependent Probe Amplification (MLPA) for Prenatal Diagnosis of Common Aneuploidies.

Multiplex Ligation-dependent Probe Amplification (MLPA) is a method to determine the copy number of up to 60 genomic DNA sequences in a single multiplex PCR based reaction.MLPA probes consist of two oligonucleotides that can hybridize next to each other on a certain DNA sequence of interest, where they are ligated. All ligated probes are subsequently amplified by PCR using a single set of primers.

Whole blood transcriptome analysis in amyotrophic lateral sclerosis: A biomarker study.

The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain elusive and diagnostic decision-making can be challenging. Gene expression studies are valuable in overcoming such challenges since they can shed light on differentially regulated pathways and may ultimately identify valuable biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients and 645 control subjects, identified 2,943 differentially expressed transcripts predominantly involved in RNA binding and intracellular transport.

Same-day subtyping of Campylobacter jejuni and C. coli isolates by use of multiplex ligation-dependent probe amplification-binary typing.

Campylobacteriosis is the most commonly reported form of human bacterial gastroenteritis in the world. Sound identification of infectious sources requires subtyping, but the most widely used methods have turnaround times measured in days and require specialist equipment and skills. A multiplex ligation-dependent probe amplification-binary typing (MBiT) assay was developed for subtyping Campylobacter jejuni and Campylobacter coli.

Analysis of the KIFAP3 gene in amyotrophic lateral sclerosis: a multicenter survival study.

Sporadic amyotrophic lateral sclerosis is a multifactorial disease of environmental and genetic origin. In a previous large multicenter genome wide study, common genetic variation in the Kinesin-Associated Protein 3 (KIFAP3) gene (rs1541160) was reported to have a significant effect on survival in amyotrophic lateral sclerosis patients. However, this could not be replicated in 3 smaller independent cohorts.

Gene expression profile of SOD1-G93A mouse spinal cord, blood and muscle.

The exact pathway leading to neuron death and muscle atrophy in amyotrophic lateral sclerosis (ALS) has not yet been elucidated. Gene expression profile of spinal cord, blood and muscle could provide signalling pathways and systemic alterations useful for future biomarker development. In our study we compared whole genome expression profiles of lumbar spinal cord with peripheral blood and tibialis anterior muscle in 16 mutant SOD1-G93A mice and 15 wild-type littermates.

Screening for rare variants in the coding region of ALS-associated genes at 9p21.2 and 19p13.3.

Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease that causes progressive muscle weakness, eventually resulting in death because of respiratory failure. Genetic variants are thought to predispose to the disease. A recent, large, genome-wide association study identified 2 loci that increase susceptibility to ALS.

H63D polymorphism in HFE is not associated with amyotrophic lateral sclerosis.

The H63D polymorphism in HFE has frequently been associated with susceptibility to amyotrophic lateral sclerosis (ALS). Regarding the role of HFE in iron homeostasis, iron accumulation is considered an important process in ALS. Furthermore, novel therapeutic strategies are being developed targeting this process.

Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.

Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. Individuals with ALS rapidly progress to paralysis and die from respiratory failure within 3 to 5 years after symptom onset. Epidemiological factors explain only a modest amount of the risk for ALS.

EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Disease onset and progression are variable, with survival ranging from months to decades. Factors underlying this variability may represent targets for therapeutic intervention.

Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative disease characterized by loss of upper and lower motor neurons. ALS is considered to be a complex trait and genome-wide association studies (GWAS) have implicated a few susceptibility loci. However, many more causal loci remain to be discovered.

NIPA1 polyalanine repeat expansions are associated with amyotrophic lateral sclerosis.

Mutations in NIPA1 cause Hereditary Spastic Paraplegia type 6, a neurodegenerative disease characterized by an (upper) motor neuron phenotype. Deletions of NIPA1 have been associated with a higher susceptibility to amyotrophic lateral sclerosis (ALS). The exact role of genetic variation in NIPA1 in ALS susceptibility and disease course is, however, not known.

Rare and common paraoxonase gene variants in amyotrophic lateral sclerosis patients.

Polymorphisms in the paraoxonase family (PON) have been reported in patients with amyotrophic lateral sclerosis (ALS), but a recent meta-analysis did not show a clear association. Recently, PON mutations have also been identified in ALS patients. In this study, we assessed the frequency of PON variants in 1118 sporadic ALS patients, 93 familial ALS patients, and 1240 control subjects of Dutch descent.

SMN1 gene duplications are associated with sporadic ALS.

Objective: To investigate the role of SMN1 and SMN2 copy number variation and point mutations in amyotrophic lateral sclerosis (ALS) pathogenesis in a large population.

Methods: We conducted a genetic association study including 847 patients with ALS and 984 controls. We used multiplexed ligation-dependent probe amplification (MLPA) assays to determine SMN1 and SMN2 copy numbers and examined effects on disease susceptibility and disease course.

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis.

Objective: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence.

UNC13A is a modifier of survival in amyotrophic lateral sclerosis.

A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in addition, modify survival, provide promising therapeutic targets in ALS, a disease whose etiology remains largely elusive.

VCP mutations in familial and sporadic amyotrophic lateral sclerosis.

Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of VCP mutations in patients with sporadic ALS, sporadic ALS-FTD, and progressive muscular atrophy (PMA), a known clinical mimic of inclusion body myopathy, is not known.

Multifocal motor neuropathy is not associated with genetic variation in PTPN22, BANK1, Blk, FCGR2B, CD1A/E, and TAG-1 genes.

The contribution of genetic heterogeneity to the pathogenesis of multifocal motor neuropathy (MMN) has not been elucidated. We investigated frequencies of single nucleotide polymorphisms (SNPs) in the candidate genes protein tyrosine phosphatase, non-receptor type 22 (PTPN22), B-cell scaffold protein with ankyrin repeats (BANK1), B lymphocyte kinase (Blk), and Fc gamma receptor class IIB (FCGR2B), which have been found to be associated with other autoimmune diseases, CD1A and CD1E, important for antigen presentation of glycolipids, and transient axonal glycoprotein 1 (TAG-1), which is associated with responsiveness to intravenous immunoglobulin in patients with chronic inflammatory demyelinating polyneuropathy. SNP frequencies were determined by means of TaqMan SNP genotyping assay and direct sequencing of candidate genes in 92 Dutch patients with MMN and 1152 healthy controls.

Novel optineurin mutations in sporadic amyotrophic lateral sclerosis patients.

Optineurin (OPTN) mutations have been reported in a cohort of Japanese patients with familial (FALS) and sporadic (SALS) amyotrophic lateral sclerosis. In Caucasian patients, OPTN mutations have been identified in FALS patients, but were not detected in a cohort of 95 SALS patients. Moreover, single nucleotide polymorphisms (SNPs) in OPTN that could raise amyotrophic lateral sclerosis (ALS) susceptibility have not been investigated.

Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2.

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons that results in progressive muscle weakness and limits survival to 2-5 years after disease onset. Intermediate CAG repeat expansions in ataxin 2 (ATXN2), the causative gene of spinocerebellar ataxia type 2 (SCA2), have been implicated in sporadic ALS. We studied ATXN2 in a large cohort of patients with sporadic and familial ALS.

A large genome scan for rare CNVs in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations.

FUS mutations in familial amyotrophic lateral sclerosis in the Netherlands.

Objectives: To assess the frequency of FUS mutations in 52 probands with familial amyotrophic lateral sclerosis (FALS) and to provide careful documentation of clinical characteristics.

Design: FUS mutation analysis was performed using capillary sequencing on all coding regions of the gene in a cohort of patients with FALS. The clinical characteristics of patients carrying FUS mutations were described in detail.

Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis.

A genome-wide association study (GWAS) using pooled DNA samples from 386 sporadic ALS patients and 542 controls from the USA, identified genetic variation in FGGY (FLJ10986) as a risk factor, as well as 66 additional candidate SNPs. Considering the large number of hypotheses that are tested in GWAS, independent replication of associations is crucial for identifying true-positive genetic risk factors for disease. The primary aim of this study was to study the association between FGGY and sporadic ALS in large, homogeneous populations from northern Europe.