The p.Cys169Tyr variant of connexin 26 is not a polymorphism.

Mutations in the GJB2 gene, which encodes the gap junction protein connexin 26 (Cx26), are the primary cause of hereditary prelingual hearing impairment. Here, the p.Cys169Tyr missense mutation of Cx26 (Cx26C169Y), previously classified as a polymorphism, has been identified as causative of severe hearing loss in two Qatari families. We have analyzed the effect of this mutation using a combination of confocal immunofluorescence microscopy and molecular dynamics simulations. At the cellular level, our results show that the mutant protein fails to form junctional channels in HeLa transfectants despite being correctly targeted to the plasma membrane. At the molecular level, this effect can be accounted for by disruption of the disulfide bridge that Cys169 forms with Cys64 in the wild-type structure (Cx26WT). The lack of the disulfide bridge in the Cx26C169Y protein causes a spatial rearrangement of two important residues, Asn176 and Thr177. In the Cx26WT protein, these residues play a crucial role in the intra-molecular interactions that permit the formation of an intercellular channel by the head-to-head docking of two opposing hemichannels resident in the plasma membrane of adjacent cells. Our results elucidate the molecular pathogenesis of hereditary hearing loss due to the connexin mutation and facilitate the understanding of its role in both healthy and affected individuals.

Increased rate of deleterious variants in long runs of homozygosity of an inbred population from Qatar.

OBJECTIVE: The aim of this study is to evaluate the fraction of putatively deleterious variants within genomic runs of homozygosity (ROH) regions in an inbred and selected cohort of Qatari individuals. METHODS: High-density SNP array analysis was performed in 36 individuals, and for 14 of them whole-exome sequencing (WES) was also carried out. RESULTS: In all individuals, regions characterized by a high (hotspot) or low (coldspot) degree of homozygosity in all the analysed individuals were mapped, and the most frequent hotspot regions were selected. WES data were exploited to identify the single nucleotide variations (SNVs) harboured by genes located within both regions in each individual. Evolutionary conservation-based algorithms were employed to predict the potential deleteriousness of SNVs. The amount of in silico predicted deleterious SNVs was significantly different (p < 0.05) between homozygosity hotspot and coldspot regions. CONCLUSION: Genes located within ROH hotspot regions contain a significant burden of predicted putatively deleterious variants compared to genes located outside these regions, suggesting inbreeding as a possible mechanism allowing an enrichment of putatively deleterious variants at the homozygous state.

Consanguinity and hereditary hearing loss in Qatar.

Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease.

Graph-Based Electroencephalography Analysis in Tinnitus Therapy.

Tinnitus is the perception of sounds like ringing or buzzing in the ears without any external source, varying in intensity and potentially becoming chronic. This study aims to enhance the understanding and treatment of tinnitus by analyzing a dataset related to tinnitus therapy, focusing on electroencephalography (EEG) signals from patients undergoing treatment. The objectives of the study include applying various preprocessing techniques to ensure data quality, such as noise elimination and standardization of sampling rates, and extracting essential features from EEG signals, including power spectral density and statistical measures. The novelty of this research lies in its innovative approach to representing different channels of EEG signals as new graph network representations without losing any information. This transformation allows for the use of Graph Neural Networks (GNNs), specifically Graph Convolutional Networks (GCNs) combined with Long Short-Term Memory (LSTM) networks, to model intricate relationships and temporal dependencies within the EEG data. This method enables a comprehensive analysis of the complex interactions between EEG channels. The study reports an impressive accuracy rate of 99.41%, demonstrating the potential of this novel approach. By integrating graph representation and deep learning, this research introduces a new methodology for analyzing tinnitus therapy data, aiming to contribute to more effective treatment strategies for tinnitus sufferers.

Interaction between diabetes mellitus and hypertension on risk of hearing loss in highly endogamous population.

AIM: The aim of this study was to determine the prevalence of hearing loss and its association with type 2 diabetes mellitus (T2DM) in a highly endogamous population. DESIGN: This is a cross-sectional study. SETTING: The present study is carried out in Ear Nose Throat (ENT) and Endocrinology outpatient clinics of the Hamad General and Rumeilah Hospitals, Hamad Medical Corporation. SUBJECTS: All subjects aged between 20 and 59 years who visited the Endocrinology and ENT outpatient clinics of the Hamad Medical Corporation with hearing difficulty were included in this study during the period from January 2013 to July 2014. METHOD: During the study period, prevalence, hearing, audiological test, family history and medical problems associated with hearing impairment in middle aged patients were recorded. Two audiometers Grason Stadler GSI 61 and Madsen Orbiter 922 were used to evaluate the hearing loss. RESULT: Majority of the hearing loss observed at the age above 45 years old, (44.8% vs 51.7%, p=0.05). The prevalence of hearing impairment was higher in Qataris than in non-Qataris (59.7% vs 46.6%, p<0.001). The consanguineous marriages were observed higher in Hearing loss (32.1%) than in normal hearing (21.8%) (p=0.028). The mean of diabetes onset duration (7.8±4.12years), sleeping disorder (5.81±1.29h), obese subjects (38% vs 27.4%); family history of diabetes (30.6 vs 23.1%) were higher among hearing impairment. The associated risk factors were significantly higher in T2DM with hearing loss, hypoglycemia (32.8% vs 27.4%), retinopathy (313% vs 18.5%), Nephropathy (17.9% vs 9.8%), Neuropathy (17.9% vs 10.2%), macro-vascular disease (11.9% vs 6.2%), diabetic foot ulcer (20.9% vs 12.6%), Tinnitus (68.7% vs 51.3%), and Vertigo (25.4% vs 16.9%) than in normal hearing diabetes. There was a statistically significant differences between hearing impairment and normal hearing among T2DM regarding hearing assessment frequency (p=0.041). There were statistically significant differences between hearing impairment versus normal hearing for vitamin D [18.91±7.65ng/mL vs 22.85±9.00ng/mL; p<0.001], calcium [1.80±0.12ng/mL vs 1.96±0.14mmol/L; p<0.001], magnesium [0.80±0.09mmol/L vs 0.8±0.14mmol/L; p<0.001], phosphorous [1.42±0.30mmol/L vs 1.56±0.26mmol/L; p<0.001], ceatinine [1.42±0.30mmol/L vs 1.56±0.26mmol/L; p<0.001], cholesterol [4.92±1.08mmol/L vs 4.40±1.01mmol/L; p=0.035], LDL [1.92±0.88mmol/L vs 2.09±0.92mmol/L; p=0.024], albumin [43.1±6.10mmol/L vs 39.8±7.93mmol/L; p=0.010], systolic blood pressure [135.8±16.6Hg vs 130.2±12.5Hg; p=0.017] and, diastolic blood pressure [85.1±9.2mmHg vs 83.0±7.9mmHg; p=0.012]. There were highly statistically significant differences between hearing impairment versus normal for both side right and left ear frequency in Db unit (p<0.001). The multivariate stepwise logistic regression analysis revealed that head ache (p<0.001), family history of DM (p<0.001), sleep disturbance (p<0.001), high blood pressure (p=0.006), consanguinity (p=0.010), nationality (p=0.014), age in years (p=0.025), and sheesha smokers (p=0.045) were considered at higher risk as a predictors of hearing loss among diabetic patients. CONCLUSION: The current study results confirm previous reports that adults with DM and hypertension associated showed greater hearing impairment in highly endogamous population… Diabetic patients with hearing loss were likely to have high blood glucose and other risk factors like hypertension, retinopathy, nephropathy and neuropathy.

Targeted sequencing identifies novel variants involved in autosomal recessive hereditary hearing loss in Qatari families.

Hereditary hearing loss is characterized by a very high genetic heterogeneity. In the Qatari population the role of GJB2, the worldwide HHL major player, seems to be quite limited compared to Caucasian populations. In this study we analysed 18 Qatari families affected by non-syndromic hearing loss using a targeted sequencing approach that allowed us to analyse 81 genes simultaneously. Thanks to this approach, 50% of these families (9 out of 18) resulted positive for the presence of likely causative alleles in 6 different genes: CDH23, MYO6, GJB6, OTOF, TMC1 and OTOA. In particular, 4 novel alleles were detected while the remaining ones were already described to be associated to HHL in other ethnic groups. Molecular modelling has been used to further investigate the role of novel alleles identified in CDH23 and TMC1 genes demonstrating their crucial role in Ca2+ binding and therefore possible functional role in proteins. Present study showed that an accurate molecular diagnosis based on next generation sequencing technologies might largely improve molecular diagnostics outcome leading to benefits for both genetic counseling and definition of recurrence risk.

Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss.

Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes involved in deafness have not yet been identified. Therefore, there remains a need to search for new causative mutations. In this study, a combined strategy using both linkage analysis and sequencing identified a new mutation causing hearing loss. Linkage analysis identified a region of 40 Mb on chromosome 5q13 (LOD score 3.8) for which exome sequencing data revealed a mutation (c.7873 T>G leading to p.*2625Gluext*11) in the BDP1 gene (B double prime 1, subunit of RNA polymerase III transcription initiation factor IIIB) in patients from a consanguineous Qatari family of second degree, showing bilateral, post-lingual, sensorineural moderate to severe hearing impairment. The mutation disrupts the termination codon of the transcript resulting in an elongation of 11 residues of the BDP1 protein. This elongation does not contain any known motif and is not conserved across species. Immunohistochemistry studies carried out in the mouse inner ear showed Bdp1 expression within the endothelial cells in the stria vascularis, as well as in mesenchyme-derived cells surrounding the cochlear duct. The identification of the BDP1 mutation increases our knowledge of the molecular bases of Nonsyndromic Hereditary Hearing Loss and provides new opportunities for the diagnosis and treatment of this disease in the Qatari population.

Low-level laser therapy in patients with complaints of tinnitus: a clinical study.

Objective. The objective of the study was to investigate the effectiveness of low-level laser therapy (LLLT) in treating patients who were suffering from long-term complaints of tinnitus with well-understood etiology and who were not responding to conventional therapy in Qatar. Design. This is a prospective clinical study conducted during the period from May 2010 and February 2011. Setting. Audiology Clinic, Outpatient Department, Hamad General Hospital. Subjects and Methods. The study included 65 patients aged 15-76 years with chronic unilateral or bilateral tinnitus with a minimum duration of illness of one year. The investigation included 101 ears of 65 patients. A 5 mW laser with a wavelength of 650 nm was applied transmeatally for 20 minutes once daily for 3 months. The study was based on a face-to-face interview with a designed questionnaire that recorded the diagnosis of patients, clinical evaluation and audiometric test results, and side effects of low-level laser therapy (LLLT) and scored their symptoms loudness on five-point scale every two weeks. A decrease of one scale point regarding the loudness duration and degree of annoyance of tinnitus was accepted to represent an improvement; at the same time, a pure tone audiometric test was carried out and the results recorded. In addition, a record of the side effect was taken. Results. Over half of the patients (56.9%) had some form of improvement in their tinnitus symptoms. Mild improvement was reported in 33.8% of patients, moderate improvement was reported in 16.9%, and full improvement was reported in 6.15%. Of the patients who reported dizzy spells as a symptom of their tinnitus condition, 27.7% reported mild improvement and 16.9% reported full improvement. Common side effects of LLLT were noted among 20% of patients; however, all of them were mild and disappeared within a few days. Conclusion. Low-level laser therapy was found to be useful for treatment of chronic tinnitus.

Results of intravenous steroid injection on reduction of postoperative edema in rhinoplasty.

OBJECTIVE: To determine the efficacy of intravenous dexamethasone in reducing postrhinoplasty edema. DESIGN: A prospective, randomized clinical trial with placebo control. SETTING: Department of Otorhinolaryngology, Al-Sabah and Zain Hospital, Kuwait. SUBJECT: Eighty-four patients (male = 28; female = 56) aged between 20 and 40 years, undergoing open rhinoplasty with hump removal and bilateral lateral osteotomies were enrolled in this study. INTERVENTION: Patients were randomized to receive two doses of 10 mg of dexamethasone intravenously or placebo, first dose during surgery and second dose 12 hours after surgery. MAIN OUTCOME MEASURES: Patients were evaluated postoperatively at 24 hours, days 2, 5, 7 and 10 for periorbital edema. RESULTS: 10 mg of dexamethasone given intravenously during rhinoplasty and a second dose 12 hours after surgery, reduced postoperative periorbital edema significantly. CONCLUSION: This study showed a statistically significant benefit of dexamethasone over placebo in reducing periorbital edema after rhinoplasty. No complications were attributed to the administration of dexamethasone.

Unusual malignant transformation of recurrent sebaceoma. A case report.

Sebaceoma is a benign tumor composed of incompletely differentiated sebaceous cells of varying degrees of maturity. Sebaceomas was never reported as a known premalignant lesion.This is a report of a sixteen year old boy who presented with a malignant transformation of a recurrent sebaceoma which was excised twice by Moh's surgery. Excision was done with a free margin of 1 cm down to the parotid fascia. Reconstruction was performed on the same set by using cervicofascial flap extending down to the supra-clavicular area. The patient had an uneventful postoperative period apart from distal marginal necrosis of the flap, which healed nicely with conservative measures and daily dressing and was sent to our cancer centre to start his adjuvant radiotherapy.Previous literature stated that sebaceoma is a distinctive benign tumor. We have presented a case of an unusual malignant transformation of a preauricular recurrent sebaceoma. This indicates that sebaceoma does have a potential risk of malignant transformation. We believe that managing recurrent sebaceoma more aggressively with wide local excision and postoperative adjuvant radiotherapy would provide better prognosis.

Evaluation of vestibular evoked myogenic potentials.

In previous studies, electromyographic potentials, recorded in response to auditory clicks, have been attributed to stimulation of the otolith (saccule) and have been termed vestibular evoked myogenic potentials (VEMPs). In this study, we assessed the VEMPs in subjects with normal auditory brainstem evoked responses, with no history of vestibular symptoms or neck and other skeletal muscle abnormalities. To this effect, 32 subjects (64 ears), after ethics committee approval, were exposed to 75, 150, and 300 clicks at 100 dB, and the responses were averaged. Electromyographic activity was recorded by applying surface electrodes over the sternocleiodomastoid muscle under the following three conditions: no muscle contraction/no clicks, muscle contraction/no clicks, and muscle contraction/clicks. Our findings suggest that electromyographic responses have to be obtained, during muscle contraction, first without and then with clicks. Our data also suggest that comparison of these two recordings is necessary for meaningful results.