Exome variant prioritization in a large cohort of hearing-impaired individuals indicates IKZF2 to be associated with non-syndromic hearing loss and guides future research of unsolved cases.

Although more than 140 genes have been associated with non-syndromic hereditary hearing loss (HL), at least half of the cases remain unexplained in medical genetic testing. One reason is that pathogenic variants are located in 'novel' deafness genes. A variant prioritization approach was used to identify novel (candidate) genes for HL.

[The value of re-evaluation and thorough family history taking for the diagnostic work-up of chorea].

The differential diagnosis of chorea encompasses a broad range of disorders. In psychiatry, tardive dyskinesia may be difficult to discern from other causes, particularly when the family history is negative. A 59-year-old man with an unclear medical history had been using risperidone for over a decade when we first saw him.

Osseointegration of a hydroxyapatite-coated stem in femoral neck fractures in the over-80 s.

Purpose: In the over-80 s, femoral bone is often osteoporotic and unlikely to be conducive to periprosthetic bone rehabitation. This observation often leads to cemented fixation for hemiarthroplasty in femoral neck fracture. Hydroxyapatite is a bioactive coating that has already demonstrated its osteoinductive properties.

Generation and Characterization of a Zebrafish Model for Associated Retinal Dysfunction Using CRISPR/Cas9 Genome Editing Technology.

Worldwide, around 40,000 people progressively lose their eyesight as a consequence of retinitis pigmentosa (RP) caused by pathogenic variants in the gene, for which currently no treatment options exist. A model organism that mimics the human phenotype is essential to unravel the exact pathophysiological mechanism underlying associated RP, and to evaluate future therapeutic strategies. The introduction of CRISPR/Cas-based genome editing technologies significantly improved the possibilities of generating mutant models in a time- and cost-effective manner.

A protein domain-oriented approach to expand the opportunities of therapeutic exon skipping for -associated retinitis pigmentosa.

Loss-of-function mutations in are among the most common causes of syndromic and non-syndromic retinitis pigmentosa (RP). We previously presented skipping of exon 13 as a promising treatment paradigm for -associated RP. However, RP-associated mutations are often private, and evenly distributed along the gene.

Exploring Primary Healthcare Experiences and Interest in Mobile Technology Engagement Amongst an Urban Population Experiencing Barriers to Care.

Mobile phone-based engagement approaches provide potential platforms for improving access to primary healthcare (PHC) services for underserved populations. We held two focus groups (February 2020) with residents ( = 25) from a low-income urban neighbourhood (downtown Vancouver, Canada), to assess recent healthcare experiences and elicit interest in mobile phone-based healthcare engagement for underserved residents. Note-based analysis, guided by interpretative description, was used to explore emerging themes.

Analysis of Rotterdam Study cohorts confirms a previously identified in-frame deletion as a prevalent genetic factor in phenotypically variable adult-onset hearing loss (DFNA21) in the Netherlands.

Background: A 12-nucleotide in-frame deletion was recently identified as a relatively common and highly penetrant cause of autosomal dominant non-syndromic sensorineural hearing loss, type DFNA21, in the Netherlands. The associated hearing phenotype is variable. The allele frequency (AF) of 0.

Genotype and Phenotype Analyses of a Novel Variant (c.2512C>T p.(Pro838Ser)) Associated with DFNA6/14/38.

The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch-German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband.

Whole genome sequencing for -associated disease reveals several pathogenic deep-intronic variants that are amenable to splice correction.

A significant number of individuals with a rare disorder such as Usher syndrome (USH) and (non-)syndromic autosomal recessive retinitis pigmentosa (arRP) remain genetically unexplained. Therefore, we assessed subjects suspected of -associated disease and no or mono-allelic variants using whole genome sequencing (WGS) followed by an improved pipeline for variant interpretation to provide a conclusive diagnosis. One hundred subjects were screened using WGS to identify causative variants in or other USH/arRP-associated genes.

Compact holographic sound fields enable rapid one-step assembly of matter in 3D.

Acoustic waves exert forces when they interact with matter. Shaping ultrasound fields precisely in 3D thus allows control over the force landscape and should permit particulates to fall into place to potentially form whole 3D objects in "one shot." This is promising for rapid prototyping, most notably biofabrication, since conventional methods are typically slow and apply mechanical or chemical stress on biological cells.

Optical genome mapping and revisiting short-read genome sequencing data reveal previously overlooked structural variants disrupting retinal disease-associated genes.

Purpose: Structural variants (SVs) play an important role in inherited retinal diseases (IRD). Although the identification of SVs significantly improved upon the availability of genome sequencing, it is expected that involvement of SVs in IRDs is higher than anticipated. We revisited short-read genome sequencing data to enhance the identification of gene-disruptive SVs.

Minigene-Based Splice Assays Reveal the Effect of Non-Canonical Splice Site Variants in .

Non-canonical splice site variants are increasingly recognized as a relevant cause of the -associated diseases, non-syndromic autosomal recessive retinitis pigmentosa and Usher syndrome type 2. Many non-canonical splice site variants have been reported in public databases, but an effect on pre-mRNA splicing has only been functionally verified for a subset of these variants. In this study, we aimed to extend the knowledge regarding splicing events by assessing a selected set of non-canonical splice site variants and to study their potential pathogenicity.

Affinity purification of in vivo assembled whirlin-associated protein complexes from the zebrafish retina.

Mutations in WHRN lead to Usher syndrome type 2d or to non-syndromic hearing impairment. The WHRN-encoded gene product whirlin directly interacts with the intracellular regions of the other two Usher syndrome type 2-associated proteins, usherin and ADGRV1. In photoreceptor cells, this protein complex constitutes fibrous links between the periciliary membrane and the connecting cilium.

Scrutinizing pathogenicity of the USH2A c.2276 G > T; p.(Cys759Phe) variant.

The USH2A variant c.2276 G > T (p.(Cys759Phe)) has been described by many authors as a frequent cause of autosomal recessive retinitis pigmentosa (arRP).

Genetics of Hearing Impairment.

The inner ear is a complex structure at the cellular and molecular levels [...

A resting-state fMRI pattern of spinocerebellar ataxia type 3 and comparison with F-FDG PET.

Spinocerebellar ataxia type 3 (SCA3) is a rare genetic neurodegenerative disease. The neurobiological basis of SCA3 is still poorly understood, and up until now resting-state fMRI (rs-fMRI) has not been used to study this disease. In the current study we investigated (multi-echo) rs-fMRI data from patients with genetically confirmed SCA3 (n = 17) and matched healthy subjects (n = 16).

Listening to bluetooth beacons for epidemic risk mitigation.

The ongoing COVID-19 pandemic let to efforts to develop and deploy digital contact tracing systems to expedite contact tracing and risk notification. Unfortunately, the success of these systems has been limited, partly owing to poor interoperability with manual contact tracing, low adoption rates, and a societally sensitive trade-off between utility and privacy. In this work, we introduce a new privacy-preserving and inclusive system for epidemic risk assessment and notification that aims to address these limitations.

Usher syndrome type IV: clinically and molecularly confirmed by novel ARSG variants.

Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (ARSG) gene have been reported to underlie USH type IV.

Generation of Humanized Zebrafish Models for the In Vivo Assessment of Antisense Oligonucleotide-Based Splice Modulation Therapies.

Antisense oligonucleotide (AON)-based splice modulation is the most widely used therapeutic approach to redirect precursor messenger RNA (pre-mRNA) splicing. To study the functional effect of human mutations affecting pre-mRNA splicing for which AON-based splice redirection would be a potential therapeutic option, humanized knock-in animal models are pivotal. A major limitation of using humanized animal models for this purpose is the reported poor recognition of human splice sites by the splicing machineries of other species.