SORT1 Mutation Resulting in Sortilin Deficiency and p75^NTR Upregulation in a Family With Essential Tremor

Abstract

*These authors contributed equally to this work.Essential tremor (ET) is the most prevalent movement disorder affecting millions of people in the United States. Although a positive family history is one of the most important risk factors for ET, the genetic causes of ET remain unknown. In this study, whole exome sequencing and subsequent approaches were performed in a family with an autosomal dominant form of early-onset ET. Functional analyses including mutagenesis, cell culture, gene expression, enzyme-linked immunosorbent, and apoptosis assays were also performed. A disease-segregating mutation (p.Gly171Ala), absent in normal population, was identified in the SORT1 gene. The p.Gly171Ala mutation was shown not only to impair the expression of its encoding protein sortilin but also the mRNA levels of its binding partner p75 neurotrophin receptor that is known to be implicated in brain injury, neuronal apoptosis, and neurotransmission.

microRNA from brush biopsy to characterize oral squamous cell carcinoma epithelium

“…SORT1 mRNA was also decreased. A decrease in SORT1 may play a role in the increase in the low‐affinity nerve growth receptor p75TNR that is often seen with OSCC . The oncogene BCL2 mRNA counterintuitively was decreased, as was the high‐affinity nerve growth receptor mRNA, NTRK2.…”

Automatic Analysis of Archimedes’ Spiral for Characterization of Genetic Essential Tremor Based on Shannon’s Entropy and Fractal Dimension

“…Subjects were selected among patients of a previous study that comprises familiar and sporadic ET cases, whereas control individuals were recruited in the Movement Disorders Unit of the Donostia University Hospital (in San Sebastian, Spain). A new informed consent was signed by every participant in our study, which was approved by the ethics committee of the Donostia University Hospital [ 25 , 26 ]. For each individual, an electrophysiological test (EPT) and fMRI are available.…”

“…The work presented in this paper is part of a larger cross study aimed at diagnosing and characterizing essential tremor. This research is conducted at the Biodonostia Health Institute, and it analyzes families with identified genetic loci [ 25 , 26 ]. Nevertheless, the study presented in the manuscript is aimed at the characterization of essential tremor, and its objectives are focused on establishing the limits related to the natural variability of ET and the ability to discriminate ET from physiological tremor.…”

Identification of a LargeDNAJB2Deletion in a Family with Spinal Muscular Atrophy and Parkinsonism

“…Table S1). All qPCR assays were performed on an Eco Real‐Time PCR System (Illumina Inc, San Diego, CA, USA), as described elsewhere [Sanchez, et al., ].…”