Transcriptomic Changes Resulting From Overexpression Identify Pathways Potentially Relevant to Essential Tremor.

Essential tremor (ET) is a common movement disorder that has a high heritability. A number of genetic studies have associated different genes and loci with ET, but few have investigated the biology of any of these genes. was significantly associated with ET in a large genome-wide association study (GWAS) and was found to be overexpressed in ET cerebellar tissue.

Multiomics Analyses Identify Genes and Pathways Relevant to Essential Tremor.

Introduction: The genetic factors and molecular mechanisms predisposing to essential tremor (ET) remains largely unknown.

Objective: The objective of this study was to identify pathways and genes relevant to ET by integrating multiomics approaches.

Methods: Case-control RNA sequencing of 2 cerebellar regions was done for 64 samples.

Heterozygous Missense Pathogenic Variants Within the Second Spectrin Repeat of SPTBN2 Lead to Infantile-Onset Cerebellar Ataxia.

The term encompasses a heterogeneous group of neurodegenerative disorders due to pathogenic variants in more than 100 genes, underlying 2 major groups of ataxia: autosomal dominant cerebellar ataxias (ADCA, also known as spinocerebellar ataxias [SCAs]) due to heterozygous variants or polyglutamine triplet expansions leading to adult-onset ataxia, and autosomal recessive spinocerebellar ataxias (ARCAs, also known as SCARs) due to biallelic variants, usually resulting in more severe and earlier-onset cerebellar ataxia. Certain ataxia genes, including which encodes β-III spectrin, are responsible for both SCA and SCAR, depending on whether the pathogenic variant occurs in a monoallelic or biallelic state, respectively. Accordingly, 2 major phenotypes have been linked to : pathogenic heterozygous in-frame deletions and missense variants result in an adult-onset, slowly progressive ADCA (SCA5) through a dominant negative effect, whereas biallelic loss-of-function variants cause SCAR14, an allelic disorder characterized by infantile-onset cerebellar ataxia and cognitive impairment.

Transcriptome-wide association study of attention deficit hyperactivity disorder identifies associated genes and phenotypes.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental psychiatric disorder. Genome-wide association studies (GWAS) have identified several loci associated with ADHD. However, understanding the biological relevance of these genetic loci has proven to be difficult.

Pathogenic variants in AIMP1 cause pontocerebellar hypoplasia.

Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is a non-catalytic component of the multi-tRNA synthetase complex which catalyzes the ligation of amino acids to the correct tRNAs. Pathogenic variants in several aminoacyl-tRNA synthetases genes have been linked to various neurological disorders, including leukodystrophies and pontocerebellar hypoplasias (PCH). To date, loss-of-function variants in AIMP1 have been associated with hypomyelinating leukodystrophy-3 (MIM 260600).