scholarly journals GJB4 and GJC3 variants in non-syndromic hearing impairment in Ghana

2020 ◽  
Vol 245 (15) ◽  
pp. 1355-1367 ◽  
Author(s):  
Samuel M Adadey ◽  
Kevin K Esoh ◽  
Osbourne Quaye ◽  
Geoffrey K Amedofu ◽  
Gordon A Awandare ◽  
...  
Keyword(s):  
Hearing Impairment ◽  
Hearing Impaired ◽  
The Body ◽  
Wild Type ◽  
Mutant Proteins ◽  
Coding Regions ◽  
Multiplex Families ◽  
Schools For The Deaf ◽  
Syndromic Hearing Impairment ◽  
Study Participants

The contribution of GJB4 and GJC3 gene variants to hearing impairment in Africa has not yet been studied. Here, we investigated the contribution of these genes to autosomal recessive non-syndromic hearing impairment in Ghanaian children. Hearing-impaired children from 141 simplex and 59 multiplex families were enrolled from 11 schools for the deaf in Ghana. The coding regions of GJB4 and GJC3 were amplified, sequenced, and analyzed for the study participants previously found to be negative for GJB2 and GJB6 variants. Seven GJB4 and one GJC3 variants were identified. One out of the seven GJB4 variants was classified as likely pathogenic, while the others were either benign or synonymous. The likely pathogenic variant (p.Asn119Thr/rs190460237) was predicted to be likely associated with hearing impairment. We modeled the wild-type and mutant proteins of this variant (p.Asn119Thr) to evaluate the effect of the mutation on protein structure and ligand-binding properties. The mutant and not the wild type had the potential to bind N-Ethyl-5ʹ-Carboxamido Adenosine (DB03719) which was due to a slight structural change that was observed. No clinically relevant variant was identified in the GJC3 gene. We report for the first time a likely pathogenic GJB4 variant that may be associated with non-syndromic hearing impairment in Ghana; the finding will add to the body of evidence of the contribution of GJB4 to hearing impairment cases around the world. Impact statement Although connexins are known to be the major genetic factors associated with HI, only a few studies have investigated GJB4 and GJC3 variants among hearing-impaired patients. This study is the first to report GJB4 and GJC3 variants from an African HI cohort. We have demonstrated that GJB4 and GJC3 genes may not contribute significantly to HI in Ghana, hence these genes should not be considered for routine clinical screening in Ghana. However, it is important to study a larger population to determine the association of GJB4 and GJC3 variants with HI.

scholarly journals Evidence for Central Asian Origin of the p.Val27Ile Variant in the GJB2 Gene

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Guille García Sánchez ◽  
Alfonso Alfaro-Rodríguez ◽  
Adrián Poblano
Keyword(s):  
Hearing Impairment ◽  
Mexico City ◽  
Common Ancestor ◽  
Gjb2 Gene ◽  
Wild Type ◽  
Altai Republic ◽  
Asian Origin ◽  
Mexican Mestizo ◽  
Central Asian ◽  
Syndromic Hearing Impairment

The mutations in the GJB2 gene are the most common cause of nonsyndromic hearing impairment and they are associated with the population’s ethnic background. The p.Val27Ile is frequent in both Asia and America. In this retrospective study, we report the findings from the GJB2 screening and the audiological exams conducted on 125 Mexican mestizo patients with non-syndromic hearing impairment; they were treated at the Instituto Nacional de Rehabilitacion in Mexico City. The most frequent audiometric findings were bilateral, symmetrical, and profound hearing impairment. The allele frequencies in the GJB2 screening were p.Val27Ile 15%, other mutations 5%, and wild type 80%. We found no correlation between GJB2 genotype and auditory phenotype. The high allele frequency of p.Val27Ile was a very interesting finding. Our research suggests that p.Val27Ile arose in an ancient common ancestor who lived in Altai Republic and then the polymorphism was brought to America by its first inhabitants, the Amerindians. These results enhance our understanding of the peopling of the America, which remains unresolved.

scholarly journals A deep intronic splice mutation of STAT3 underlies hyper IgE syndrome by negative dominance

2019 ◽  
Vol 116 (33) ◽  
pp. 16463-16472 ◽  
Author(s):  
Joëlle Khourieh ◽  
Geetha Rao ◽  
Tanwir Habib ◽  
Danielle T. Avery ◽  
Alain Lefèvre-Utile ◽  
...  
Keyword(s):  
Dominant Negative ◽  
Loss Of Function ◽  
Wild Type ◽  
Dominant Form ◽  
Mutant Proteins ◽  
Coding Regions ◽  
Hyper Ige Syndrome ◽  
Autosomal Dominant Form ◽  
Negative Dominance ◽  
B And T Lymphocytes

Heterozygous in-frame mutations in coding regions of human STAT3 underlie the only known autosomal dominant form of hyper IgE syndrome (AD HIES). About 5% of familial cases remain unexplained. The mutant proteins are loss-of-function and dominant-negative when tested following overproduction in recipient cells. However, the production of mutant proteins has not been detected and quantified in the cells of heterozygous patients. We report a deep intronic heterozygous STAT3 mutation, c.1282-89C>T, in 7 relatives with AD HIES. This mutation creates a new exon in the STAT3 complementary DNA, which, when overexpressed, generates a mutant STAT3 protein (D427ins17) that is loss-of-function and dominant-negative in terms of tyrosine phosphorylation, DNA binding, and transcriptional activity. In immortalized B cells from these patients, the D427ins17 protein was 2 kDa larger and 4-fold less abundant than wild-type STAT3, on mass spectrometry. The patients’ primary B and T lymphocytes responded poorly to STAT3-dependent cytokines. These findings are reminiscent of the impaired responses of leukocytes from other patients with AD HIES due to typical STAT3 coding mutations, providing further evidence for the dominance of the mutant intronic allele. These findings highlight the importance of sequencing STAT3 introns in patients with HIES without candidate variants in coding regions and essential splice sites. They also show that AD HIES-causing STAT3 mutant alleles can be dominant-negative even if the encoded protein is produced in significantly smaller amounts than wild-type STAT3.

Hearing Aid Amplification Reduces Communication Effort of People With Hearing Impairment and Their Conversation Partners

2020 ◽  
Vol 63 (4) ◽  
pp. 1299-1311 ◽  
Author(s):  
Timothy Beechey ◽  
Jörg M. Buchholz ◽  
Gitte Keidser
Keyword(s):  
Hearing Impairment ◽  
Hearing Aid ◽  
Normal Hearing ◽  
Referential Communication ◽  
Hearing Impaired ◽  
Directional Hearing ◽  
Acoustic Environment ◽  
Communication Task ◽  
Acoustic Environments ◽  
The Impact

Objectives This study investigates the hypothesis that hearing aid amplification reduces effort within conversation for both hearing aid wearers and their communication partners. Levels of effort, in the form of speech production modifications, required to maintain successful spoken communication in a range of acoustic environments are compared to earlier reported results measured in unaided conversation conditions. Design Fifteen young adult normal-hearing participants and 15 older adult hearing-impaired participants were tested in pairs. Each pair consisted of one young normal-hearing participant and one older hearing-impaired participant. Hearing-impaired participants received directional hearing aid amplification, according to their audiogram, via a master hearing aid with gain provided according to the NAL-NL2 fitting formula. Pairs of participants were required to take part in naturalistic conversations through the use of a referential communication task. Each pair took part in five conversations, each of 5-min duration. During each conversation, participants were exposed to one of five different realistic acoustic environments presented through highly open headphones. The ordering of acoustic environments across experimental blocks was pseudorandomized. Resulting recordings of conversational speech were analyzed to determine the magnitude of speech modifications, in terms of vocal level and spectrum, produced by normal-hearing talkers as a function of both acoustic environment and the degree of high-frequency average hearing impairment of their conversation partner. Results The magnitude of spectral modifications of speech produced by normal-hearing talkers during conversations with aided hearing-impaired interlocutors was smaller than the speech modifications observed during conversations between the same pairs of participants in the absence of hearing aid amplification. Conclusions The provision of hearing aid amplification reduces the effort required to maintain communication in adverse conditions. This reduction in effort provides benefit to hearing-impaired individuals and also to the conversation partners of hearing-impaired individuals. By considering the impact of amplification on both sides of dyadic conversations, this approach contributes to an increased understanding of the likely impact of hearing impairment on everyday communication.

Roux-en-Y Gastrointestinal Bypass Promotes Activation of TGR5 and Peptide YY

2020 ◽  
Vol 20 (8) ◽  
pp. 1262-1267
Author(s):  
Haojun Yang ◽  
Hanyang Liu ◽  
YuWen Jiao ◽  
Jun Qian
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Metabolic Diseases ◽  
Peptide Yy ◽  
The Body ◽  
Wild Type ◽  
L Cells ◽  
Body Weights ◽  
Gastrointestinal Bypass ◽  
G Protein Coupled

Background: G protein-coupled bile acid receptor (TGR5) is involved in a number of metabolic diseases. The aim of this study was to identify the role of TGR5 after Roux-en-Y gastric bypass (GBP). Methods: Wild type and TGR5 knockout mice (tgr5-/-) were fed a high-fat diet (HFD) to establish the obesity model. GBP was performed. The changes in body weight and food intake were measured. The levels of TGR5 and peptide YY (PYY) were evaluated by RT-PCR, Western blot, and ELISA. Moreover, the L-cells were separated from wild type and tgr5-/- mice. The levels of PYY in L-cells were evaluated by ELISA. Results: The body weights were significantly decreased after GBP in wild type mice (p<0.05), but not tgr5-/- mice (p>0.05). Food intake was reduced after GBP in wild type mice, but also not significantly affected in tgr5-/- mice (p>0.05). The levels of PYY were significantly increased after GBP compared with the sham group (p<0.05); however, in tgr5-/- mice the expression of PYY was not significantly affected (p>0.05). After INT-777 stimulation in L-cells obtained from murine intestines, the levels of PYY were significantly increased in L-cells tgr5+/+ (p<0.05). Conclusion: Our study suggests that GBP up-regulated the expression of TGR5 in murine intestines, and increased the levels of PYY, which further reduced food intake and decreased the body weight.

scholarly journals ‘I feel the irritation and frustration all over the body’ Affective ambiguities in networked parenting culture

2021 ◽  
pp. 136787792110035
Author(s):  
Mari Lehto ◽  
Susanna Paasonen
Keyword(s):  
Social Media ◽  
Media Use ◽  
Research Data ◽  
The Body ◽  
Social Media Use ◽  
Working Through ◽  
Media Research ◽  
Social Media Research ◽  
Study Participants

This article investigates the affective power of social media by analysing everyday encounters with parenting content among mothers. Drawing on data composed of diaries of social media use and follow-up interviews with six women, we ask how our study participants make sense of their experiences of parenting content and the affective intensities connected to it. Despite the negativity involved in reading and participating in parenting discussions, the participants find themselves wanting to maintain the very connections that irritate them, or even evoke a sense of failure, as these also yield pleasure, joy and recognition. We suggest that the ambiguities addressed in our research data speak of something broader than the specific experiences of the women in question. We argue that they point to the necessity of focusing on, and working through affective ambiguity in social media research in order to gain fuller understanding the complex appeal of platforms and exchanges.

scholarly journals Involvement of Huntingtin in Development and Ciliary Beating Regulation of Larvae of the Sea Urchin, Hemicentrotus pulcherrimus

2021 ◽  
Vol 22 (10) ◽  
pp. 5116
Author(s):  
Hideki Katow ◽  
Tomoko Katow ◽  
Hiromi Yoshida ◽  
Masato Kiyomoto
Keyword(s):  
Sea Urchin ◽  
The Body ◽  
Brdu Incorporation ◽  
Wild Type ◽  
Blastula Stage ◽  
Ciliary Beating ◽  
Marker Proteins ◽  
Disease Protein ◽  
Pattern Regulation ◽  
Hemicentrotus Pulcherrimus

The multiple functions of the wild type Huntington’s disease protein of the sea urchin Hemicentrotus pulcherrimus (Hp-Htt) have been examined using the anti-Hp-Htt antibody (Ab) raised against synthetic oligopeptides. According to immunoblotting, Hp-Htt was detected as a single band at around the 350 kDa region at the swimming blastula stage to the prism larva stage. From the 2-arm pluteus stage (2aPL), however, an additional smaller band at the 165 kDa region appeared. Immunohistochemically, Hp-Htt was detected in the nuclei and the nearby cytoplasm of the ectodermal cells from the swimming blastula stage, and the blastocoelar cells from the mid-gastrula stage. The Ab-positive signal was converged to the ciliary band-associated strand (CBAS). There, it was accompanied by several CBAS-marker proteins in the cytoplasm, such as glutamate decarboxylase. Application of Hp-Htt morpholino (Hp-Htt-MO) has resulted in shortened larval arms, accompanied by decreased 5-bromo-2-deoxyuridin (BrdU) incorporation by the ectodermal cells of the larval arms. Hp-Htt-MO also resulted in lowered ciliary beating activity, accompanied by a disordered swirling pattern formation around the body. These Hp-Htt-MO-induced deficiencies took place after the onset of CBAS system formation at the larval arms. Thus, Hp-Htt is involved in cell proliferation and the ciliary beating pattern regulation signaling system in pluteus larvae.

scholarly journals Investigation of the Stability of Yeast rad52 Mutant Proteins Uncovers Post-translational and Transcriptional Regulation of Rad52p

Genetics ◽  
2003 ◽  
Vol 163 (1) ◽  
pp. 91-101 ◽  
Author(s):  
Erin N Asleson ◽  
Dennis M Livingston
Keyword(s):  
Half Life ◽  
Translational Regulation ◽  
Cellular Level ◽  
Missense Mutations ◽  
Wild Type ◽  
Mutant Proteins ◽  
Gal1 Promoter ◽  
Rad52 Protein ◽  
The Stability ◽  
Mutant Forms

Abstract We investigated the stability of the Saccharomyces cerevisiae Rad52 protein to learn how a cell controls its quantity and longevity. We measured the cellular levels of wild-type and mutant forms of Rad52p when expressed from the RAD52 promoter and the half-lives of the various forms of Rad52p when expressed from the GAL1 promoter. The wild-type protein has a half-life of 15 min. rad52 mutations variably affect the cellular levels of the protein products, and these levels correlate with the measured half-lives. While missense mutations in the N terminus of the protein drastically reduce the cellular levels of the mutant proteins, two mutations—one a deletion of amino acids 210-327 and the other a missense mutation of residue 235—increase the cellular level and half-life more than twofold. These results suggest that Rad52p is subject to post-translational regulation. Proteasomal mutations have no effect on Rad52p half-life but increase the amount of RAD52 message. In contrast to Rad52p, the half-life of Rad51p is &gt;2 hr, and RAD51 expression is unaffected by proteasomal mutations. These differences between Rad52p and Rad51p suggest differential regulation of two proteins that interact in recombinational repair.

scholarly journals Imbalance between Expression of FOXC2 and Its lncRNA in Lymphedema-Distichiasis Caused by Frameshift Mutations

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 650
Author(s):  
Sara Missaglia ◽  
Daniela Tavian ◽  
Sandro Michelini ◽  
Paolo Enrico Maltese ◽  
Andrea Bonanomi ◽  
...  
Keyword(s):  
Mrna Stability ◽  
Healthy Subjects ◽  
Lymphatic System ◽  
System Development ◽  
Bioinformatic Analysis ◽  
Wild Type ◽  
Mutant Proteins ◽  
Frameshift Mutations ◽  
Forkhead Box ◽  
Frameshift Mutant

Forkhead-box C2 (FOXC2) is a transcription factor involved in lymphatic system development. FOXC2 mutations cause Lymphedema-distichiasis syndrome (LD). Recently, a natural antisense was identified, called lncRNA FOXC2-AS1, which increases FOXC2 mRNA stability. No studies have evaluated FOXC2 and FOXC2-AS1 blood expression in LD and healthy subjects. Here, we show that FOXC2 and FOXC-AS1 expression levels were similar in both controls and patients, and a significantly higher amount of both RNAs was observed in females. A positive correlation between FOXC2 and FOXC2-AS1 expression was found in both controls and patients, excluding those with frameshift mutations. In these patients, the FOXC2-AS1/FOXC2 ratio was about 1:1, while it was higher in controls and patients carrying other types of mutations. The overexpression or silencing of FOXC2-AS1 determined a significant increase or reduction in FOXC2 wild-type and frameshift mutant proteins, respectively. Moreover, confocal and bioinformatic analysis revealed that these variations caused the formation of nuclear proteins aggregates also involving DNA. In conclusion, patients with frameshift mutations presented lower values of the FOXC2-AS1/FOXC2 ratio, due to a decrease in FOXC2-AS1 expression. The imbalance between FOXC2 mRNA and its lncRNA could represent a molecular mechanism to reduce the amount of FOXC2 misfolded proteins, protecting cells from damage.

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