Whole-Exome Sequencing Identifies a Recurrent Small In-Frame Deletion in MYO15A Causing Autosomal Recessive Nonsyndromic Hearing Loss in 3 Iranian Pedigrees.

BACKGROUND: Hearing loss (HL) is the most prevalent and genetically heterogeneous sensory disabilities in humans throughout the world. METHODS: In this study, we used whole-exome sequencing (WES) to determine the variant causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in 3 separate Iranian consanguineous families (with 3 different ethnicities: Azeri, Persian, and Lur), followed by cosegregation analysis, computational analysis, and structural modeling using the I-TASSER (Iterative Threading ASSEmbly Refinement) server. Also, we used speech-perception tests to measure cochlear implant (CI) performance in patients. RESULTS: One small in-frame deletion variant (MYO15A c.8309_8311del (p.Glu2770del)), resulting in deletion of a single amino-acid residue was identified. We found it to be cosegregating with the disease in the studied families. We provide some evidence suggesting the pathogenesis of this variant in HL based on the American College of Medical Genetics (ACMG) and Genomics guidelines. Evaluation of auditory and speech performance indicated favorable outcome after cochlear implantation in our patients. CONCLUSIONS: The findings of this study demonstrate the utility of WES in genetic diagnostics of HL.

A novel pathogenic variant in the LRTOMT gene causes autosomal recessive non-syndromic hearing loss in an Iranian family.

BACKGROUND: Hearing loss (HL) is the most common sensorineural disorder with high phenotypic and genotypic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) constitutes a major share of HL cases. In the present study, Whole exome sequencing (WES) was applied to investigate the underlying etiology of HL in an Iranian patient with ARNSHL. METHODS: A proband from an Iranian consanguineous family was examined via WES, following GJB2 sequencing. WES was utilized to find possible genetic etiology of the disease. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Co-segregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. RESULTS: WES results showed a novel frameshift (16 bp deletion) variant (p.Ala170Alafs*20) in the LRTOMT gene. This variant, which resides in exon 6, was found to be co-segregating in the family. It fulfils the criteria set by the ACMG guidelines of being pathogenic. CONCLUSION: Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL, which is a genetically heterogeneous disorder, in a patient with ARNSHL.

The association between saliva control, silent saliva penetration, aspiration, and videofluoroscopic findings in Parkinson's disease patients.

BACKGROUND: Dysphagia is a common disorder among patients with Parkinson's disease (PD). It occurs in up to 80% of all (PD) patients during the early stages of the disease and up to 95% in the advanced stages; but professionals may not hear from the patients about dysphagia symptoms until these symptoms reach an advanced stage and lead to medical complications. MATERIALS AND METHODS: Thirty-three PD patients (mean age 66.09 ± 9.4 years; 24 men, nine women) participated in this study at our Neurology Institute, between April 20, 2013, and October 26, 2013. They were asked two questions; one about saliva control and the other about silent saliva penetration and aspiration. Next, they underwent the videofluoroscopic swallowing study (VFSS). RESULTS: The Pearson Correlation coefficient between the Penetration-Aspiration Scale (PAS) scores and question 1 scores was 0.48 (P < 0.05, =0.25), and there was a significant correlation between the PAS scores and question 2 scores, and also question 1 scores + question 2 scores (r = 0.589, P < 0.05, =0 and r = 0589, P < 0.05, =0). CONCLUSIONS: This study showed a significant correlation between the questions about saliva control, silent saliva penetration, and aspiration, and laryngeal penetration and aspiration during VFSS. Therefore, by using these two questions, the potential silent laryngeal penetration and aspiration during meals could be detected before it led to aspiration pneumonia. Taking the benefit of these questions, as a part of the swallowing assessment of PD patients, is recommended.

Validation of the persian translation of the swallowing disturbance questionnaire in Parkinson's disease patients.

Dysphagia, as a common finding in Parkinson's disease (PD) patients, was estimated to be present in 80-95% of this population during different stages of the disease. The Swallowing Disturbance Questionnaire (SDQ) was created as a self-rated dysphagia screening tool in PD. According to the guidelines for cross-cultural adaptation, Persian version of this questionnaire (SDQ-P) was developed. 59 Persian patients (39 men and 20 women) participated in the study. They responded to the SDQ-P and underwent videofluoroscopic swallowing study (VFSS). Aspiration during VFSS was compared with questionnaire results for each individual. Cronbach's alpha coefficient for the questionnaire was 0.86 and based on SDQ-P 15 patients (25.4%) were dysphagic, while 10 patients (16.9%) showed aspiration during VFSS. SDQ-P sensitivity and specificity in predicting aspiration were 96.7 and 91.2%; therefore, the SDQ-P could be a prognostic tool for aspiration. The positive predictive value (PPV), the negative predictive value (NPV), and the pre- and posttest probabilities of aspiration were 0.67, 1, 16.9%, and 66.7%, respectively. In summary, this study demonstrated the reliability and also the feasibility of SDQ-P for screening of aspiration in Iranian patients with PD. Further evaluation of SDQ-P in larger subject population would be suggested.

The occurrence of laryngeal penetration and aspiration in patients with glottal closure insufficiency.

Glottal closure during the pharyngeal phase of swallowing is one of the important steps in protecting the airway. Generally, it is believed that any deficiency in this process can lead to laryngeal penetration and aspiration. This study investigated the incidence of laryngeal penetration and aspiration among 44 patients with glottal closure insufficiencies that were referred for voice and swallowing evaluation to our institution. The videostroboscopy and 3 oz water swallow test were performed for all of the patients and dysphagic patients were screened and referred for videofluoroscopy. Overall, 15.90% of patients demonstrated signs of laryngeal penetration (13.63%) and aspiration (2.27%). The patients with the pattern of incomplete closure illustrated the highest percentage of penetration-aspiration (21.73%, 4.34%) among other GCI patterns. Thus, early interventions for these patients' swallowing condition seem necessary.

A Prevalence Study of Hearing Loss among Primary School Children in the South East of Iran.

Hearing impairment substantially affects child's ability to normally acquire the spoken language. Such negative effects create problems for the child not only in terms of communication but also in terms of achievement in school as well as social and emotional growth. The aim of this research is to study the prevalence of hearing disorders and its relationship to age and gender among primary school students of Zahedan, Iran. In this cross-sectional and descriptive analytical study, 1500 students from elementary schools were screened for hearing loss. The selection of samples was performed using multistage sampling method. Primary information was obtained through direct observation, otoscopy, and audiometric and tympanometric screenings. Data was obtained and analyzed via ANOVA test. Statistical analysis showed a significant correlation between the age and the prevalence of middle ear abnormal function. Conductive hearing loss in males and females was 8.8% and 7.1%, respectively. In addition, 1% and 0.7% of male and female students, respectively, suffered from sensorineural hearing loss. Results indicated that 20.2% of students of elementary schools in Zahedan needed medical treatment for their problems. Therefore, it is recommended that the hearing screening of school-age children should be included in annual school health programs in this region.

Ear surgery techniques results on hearing threshold improvement.

BACKGROUND: Bone conduction (BC) threshold depression is not always by means of sensory neural hearing loss and sometimes it is an artifact caused by middle ear pathologies and ossicular chain problems. In this research, the influences of ear surgeries on bone conduction were evaluated. MATERIALS AND METHODS: This study was conducted as a clinical trial study. The ear surgery performed on 83 patients classified in four categories: Stapedectomy, tympanomastoid surgery and ossicular reconstruction partially or totally; Partial Ossicular Replacement Prosthesis (PORP) and Total Ossicular Replacement Prosthesis (TORP). Bone conduction thresholds assessed in frequencies of 250, 500, 1000, 2000 and 4000 Hz pre and post the surgery. RESULTS: In stapedectomy group, the average of BC threshold in all frequencies improved approximately 6 dB in frequency of 2000 Hz. In tympanomastoid group, BC threshold in the frequency of 500, 1000 and 2000 Hz changed 4 dB (P-value < 0.05). Moreover, In the PORP group, 5 dB enhancement was seen in 1000 and 2000 Hz. In TORP group, the results confirmed that BC threshold improved in all frequencies especially at 4000 Hz about 6.5 dB. CONCLUSION: In according to results of this study, BC threshold shift was seen after several ear surgeries such as stapedectomy, tympanoplasty, PORP and TORP. The average of BC improvement was approximately 5 dB. It must be considered that BC depression might happen because of ossicular chain problems. Therefore; by resolving middle ear pathologies, the better BC threshold was obtained, the less hearing problems would be faced.