Analysis of the Ush2a Gene in Medaka Fish (Oryzias latipes)

Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the most common genetic disorder affecting hearing and vision and is included in a group of hereditary pathologies associated with defects in ciliary function known as ciliopathies. This syndrome is clinically classified into three types: USH1, USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and mutations in the USH2A gene are responsible for the majority of USH2 cases, but also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka fish (Oryzias latypes) is an attractive model organism for genetic-based studies in biomedical research, we investigated the expression and function of the USH2A ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons, containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed during early stages of medaka fish development and persists into adulthood. Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization (WMISH) on embryos at different embryonic stages showed restricted expression to otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the development and/or maintenance of retinal photoreceptors and cochlear hair cells. Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects (small eyes and heads, otolith malformations and shortened bodies with curved tails) resulting in late embryo lethality. These embryonic defects, observed in our study and in other ciliary disorders, are associated with defective cell movement specifically implicated in left-right (LR) axis determination and planar cell polarity (PCP)

Valencia’s Cathedral Church Bell Acoustics Impact on the Hearing Abilities of Bell Ringers

Studies on the effect of occupational noise have been widely performed for occupations such as construction workers, workers of factories or even musicians and workers of nightclubs. However, studies on the acoustics of church bells are very scarce and usually reported in languages other than English. In Spain, although the tradition of bell ringers is progressively getting lost, some bell ringers that continue transmitting the tradition remain. Church bells create sound with a large sound pressure level that can be heard from a great distance. However, despite the characteristics of the sound of church bells, bell ringers do not present symptoms of occupational hearing loss unlike musicians and construction workers. To determine the effects of the sound of the church bells on bell ringers, in this paper, an acoustic study of the church bells and a physiological study of the hearing abilities of bell ringers. Results show sound pressure levels reaching 120 dB inside the bell tower. The resulting hearing loss in bell ringers is small considering the great intensity of the sound produced by the bells. This is likely due to the short amount of time that bell ringers are exposed to the sound even if it reaches high sound pressure levels

Improving the Management of Patients with Hearing Loss by the Implementation of an NGS Panel in Clinical Practice

A cohort of 128 patients from 118 families diagnosed with non-syndromic or syndromic hearing loss (HL) underwent an exhaustive clinical evaluation. Molecular analysis was performed using targeted next-generation sequencing (NGS) with a custom panel that included 59 genes associated with non-syndromic HL or syndromic HL. Variants were prioritized according to the minimum allele frequency and classified according to the American College of Medical Genetics and Genomics guidelines. Variant(s) responsible for the disease were detected in a 40% of families including autosomal recessive (AR), autosomal dominant (AD) and X-linked patterns of inheritance. We identified pathogenic or likely pathogenic variants in 26 different genes, 15 with AR inheritance pattern, 9 with AD and 2 that are X-linked. Fourteen of the found variants are novel. This study highlights the clinical utility of targeted NGS for sensorineural hearing loss. The optimal panel for HL must be designed according to the spectrum of the most represented genes in a given population and the laboratory capabilities considering the pressure on healthcare

Assessment of the subjective benefit of electric acoustic stimulation with the abbreviated profile of hearing aid benefit

This study demonstrates that electric-acoustic stimulation (EAS) significantly decreases the subjective impairment in speech perception

Ultra structural architecture analysis of inner ear and stereocilia performed on MO1 morphant embryos using fluorescent staining.

<p>A. Phalloidin staining of WT larvae inner ear highlighting the three sensory areas containing stereocilia. B. Phalloidin staining of 0.1: A and B: 20 µm. C and D: 5 µm.</p

Primers used to amplify and sequence the full-length open reading frame (ORF) of <i>Ol-Ush2a</i>.

<p>Primers used to amplify and sequence the full-length open reading frame (ORF) of <i>Ol-Ush2a</i>.</p

Retinal lamination observed in WT and 0.1 mM 5 dpf morphant embryos treated with PTU.

<p>Green: Alexa-fluor-488-phalloidin: actin. Blue: TOPRO: nuclei. Red: Zpr-1: double cone photoreceptors. hc: horizontal cells. os: outer segments. is: inner segments si.</p

Medaka fish Ol-Ush2a predicted protein.

<p>Motif alignment of the human, murine, zebrafish and medaka USH2A proteins. The two lines beneath the murine Ush2a denote the two predicted variants reported (USH2A_iso_a: 170 kDa and USH2A_iso_b: 600 kDa). Symbols representing different motifs are given at the bottom of the diagram: LamGL, LamG-like jellyroll fold domain; EGF-Lam, laminin-type epidermal growth factor-like domain; FN3, fibronectin type 3; LamG, laminin G domain.</p

Evolutionary analysis of USH2A isoform_a.

<p>Alignment of the exons that correspond to the hypothetic short isoforms of <i>USH2A.</i> Only in Primates and most Eutherians the “KCV end” seems to be conserved.</p