J. Yi, Seong-Yun Ha, Hyeon-Gun Jee, Kwangsoo Kim, Su-jin Kim, Y. J. Chai, J. Choi, K. Lee
Objectives. The BRAFV600E mutation is a major driver mutation in papillary thyroid cancer. The aim of this study was to elucidate the correlation between DNA methylation and gene expression changes induced by the BRAFV600E mutation in thyroid cells. Methods. We used Nthy/BRAF cell lines generated by transfection of Nthy/ori cells with the wild-type BRAF gene (Nthy/WT cells) and the V600E mutant-type BRAF gene (Nthy/V600E cells). We performed gene expression microarray and DNA methylation array analyses for Nthy/WT and Nthy/V600E cells. Two types of array data were integrated to identify inverse correlations between methylation and gene expression. The results were verified in silico using data from The Cancer Genome Atlas (TCGA) and in vivo through pyrosequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Results. In the Nthy/V600E cells, 199,821 probes were significantly hypermethylated, and 697 genes showed a “hypermethylation-downregulation” pattern in Nthy/V600E. Tumor suppressor genes and apoptosis-related genes were included. In total, 66,446 probes were significantly hypomethylated, and 227 genes showed a “hypomethylation-upregulation” pattern in Nthy/V600E cells. Protooncogenes and developmental protein-coding genes were included. In the TCGA analysis, 491/697 (70.44%) genes showed a hypermethylation-downregulation pattern, and 153/227 (67.40%) genes showed a hypomethylation-upregulation pattern. Ten selected genes showed a similar methylation-gene expression pattern in pyrosequencing and qRT-PCR. Conclusion. Induction of the BRAFV600E mutation in thyroid cells led to frequent hypermethylation. Anticancer genes, such as those involved in tumor suppression or apoptosis, were downregulated by upstream hypermethylation, whereas carcinogenic genes, such as protooncogenes, were upregulated by hypomethylation. Our results suggest that the BRAFV600E mutation in thyroid cells modulates DNA methylation and results in cancer-related gene expression.
{"title":"Induction of the BRAFV600E Mutation in Thyroid Cells Leads to Frequent Hypermethylation","authors":"J. Yi, Seong-Yun Ha, Hyeon-Gun Jee, Kwangsoo Kim, Su-jin Kim, Y. J. Chai, J. Choi, K. Lee","doi":"10.21053/ceo.2022.00206","DOIUrl":"https://doi.org/10.21053/ceo.2022.00206","url":null,"abstract":"Objectives. The BRAFV600E mutation is a major driver mutation in papillary thyroid cancer. The aim of this study was to elucidate the correlation between DNA methylation and gene expression changes induced by the BRAFV600E mutation in thyroid cells. Methods. We used Nthy/BRAF cell lines generated by transfection of Nthy/ori cells with the wild-type BRAF gene (Nthy/WT cells) and the V600E mutant-type BRAF gene (Nthy/V600E cells). We performed gene expression microarray and DNA methylation array analyses for Nthy/WT and Nthy/V600E cells. Two types of array data were integrated to identify inverse correlations between methylation and gene expression. The results were verified in silico using data from The Cancer Genome Atlas (TCGA) and in vivo through pyrosequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Results. In the Nthy/V600E cells, 199,821 probes were significantly hypermethylated, and 697 genes showed a “hypermethylation-downregulation” pattern in Nthy/V600E. Tumor suppressor genes and apoptosis-related genes were included. In total, 66,446 probes were significantly hypomethylated, and 227 genes showed a “hypomethylation-upregulation” pattern in Nthy/V600E cells. Protooncogenes and developmental protein-coding genes were included. In the TCGA analysis, 491/697 (70.44%) genes showed a hypermethylation-downregulation pattern, and 153/227 (67.40%) genes showed a hypomethylation-upregulation pattern. Ten selected genes showed a similar methylation-gene expression pattern in pyrosequencing and qRT-PCR. Conclusion. Induction of the BRAFV600E mutation in thyroid cells led to frequent hypermethylation. Anticancer genes, such as those involved in tumor suppression or apoptosis, were downregulated by upstream hypermethylation, whereas carcinogenic genes, such as protooncogenes, were upregulated by hypomethylation. Our results suggest that the BRAFV600E mutation in thyroid cells modulates DNA methylation and results in cancer-related gene expression.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"273 - 282"},"PeriodicalIF":3.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44038284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives This study aimed to present our experiences with various approaches for endoscopic thyroidectomy (ET) and to offer lessons for choosing an approach. Methods The medical records of 701 patients who underwent ET via the transaxillary (TA), bilateral axillo-breast (BABA), unilateral axillo-breast with carbon dioxide insufflation (UABA), retroauricular (RA), or transoral vestibular (TO) approach between May 2008 and March 2020 were retrospectively reviewed. Postoperative pain and cosmetic outcomes were evaluated using visual analog scales. Results The mean operative time of UABA was the shortest among the five approaches (TA, 194.65±51.13 minutes; BABA, 189.11±61.53 minutes; UABA, 118.62±30.23 minutes; RA, 168.22±45.63 minutes; TO, 196.10±40.19 minutes; P=0.02). BABA was the most painful approach, while TO was the least painful on postoperative day 1 (TA, 3.09±0.96; BABA, 3.59±0.92; UABA, 2.39±0.54; RA, 3.49±0.93; TO, 2.01±0.37; P=0.04) and day 3 (TA, 2.10±0.77; BABA, 2.59±0.88; UABA, 1.84±0.37; RA, 3.01±0.67; TO, 1.49±0.45; P=0.04). The TO group had the best cosmetic outcomes at 3 months (TA, 3.91±1.21; BABA, 4.52±1.13; UABA, 4.49±0.74; RA, 4.28±0.74; TO, 4.81±0.48; P=0.04). Conclusion We present a single-surgeon experience of five distinctive ET approaches and the lessons from each approach, together with a literature review. This data may aid endoscopic thyroid surgeons in choosing from various ET approaches.
{"title":"Comparative Study of Gasless Transaxillary, Bilateral Axillo-Breast, Unilateral Axillo-Breast With Carbon Dioxide Insufflation, Retroauricular, and Transoral Vestibular Endoscopic Thyroidectomy Approaches at a Single Institution: A Retrospective Analysis and Lessons Learned","authors":"M. Lee, J. Ahn, I. Choi, Byeong‐Cheol Lee, J. Ryu","doi":"10.21053/ceo.2021.02285","DOIUrl":"https://doi.org/10.21053/ceo.2021.02285","url":null,"abstract":"Objectives This study aimed to present our experiences with various approaches for endoscopic thyroidectomy (ET) and to offer lessons for choosing an approach. Methods The medical records of 701 patients who underwent ET via the transaxillary (TA), bilateral axillo-breast (BABA), unilateral axillo-breast with carbon dioxide insufflation (UABA), retroauricular (RA), or transoral vestibular (TO) approach between May 2008 and March 2020 were retrospectively reviewed. Postoperative pain and cosmetic outcomes were evaluated using visual analog scales. Results The mean operative time of UABA was the shortest among the five approaches (TA, 194.65±51.13 minutes; BABA, 189.11±61.53 minutes; UABA, 118.62±30.23 minutes; RA, 168.22±45.63 minutes; TO, 196.10±40.19 minutes; P=0.02). BABA was the most painful approach, while TO was the least painful on postoperative day 1 (TA, 3.09±0.96; BABA, 3.59±0.92; UABA, 2.39±0.54; RA, 3.49±0.93; TO, 2.01±0.37; P=0.04) and day 3 (TA, 2.10±0.77; BABA, 2.59±0.88; UABA, 1.84±0.37; RA, 3.01±0.67; TO, 1.49±0.45; P=0.04). The TO group had the best cosmetic outcomes at 3 months (TA, 3.91±1.21; BABA, 4.52±1.13; UABA, 4.49±0.74; RA, 4.28±0.74; TO, 4.81±0.48; P=0.04). Conclusion We present a single-surgeon experience of five distinctive ET approaches and the lessons from each approach, together with a literature review. This data may aid endoscopic thyroid surgeons in choosing from various ET approaches.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"283 - 291"},"PeriodicalIF":3.0,"publicationDate":"2022-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41976980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Active Surveillance or Surgery in Papillary Thyroid Microcarcinoma: An Ongoing Controversy","authors":"Ho-Ryun Won, B. Koo","doi":"10.21053/ceo.2022.00605","DOIUrl":"https://doi.org/10.21053/ceo.2022.00605","url":null,"abstract":"a","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"123 - 124"},"PeriodicalIF":3.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45541554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives Nonsurgical rhinoplasty using threads has gained popularity in recent years. While the benefits of this procedure have been emphasized, possible complications and their management are not well-known. This study aimed to present the surgical management and results of the complications of thread rhinoplasty. Methods We retrospectively reviewed the medical records of seven patients who underwent revision rhinoplasty due to the complications of thread rhinoplasty from January 2018 to May 2021. The presentation of complications, detailed surgical procedures, and outcomes of revision rhinoplasty were reviewed. Results Visible or extruded threads at the tip were the most common complication, followed by dorsum irregularity. All the threads were unabsorbed and intact in shape, even several years after insertion. Thread removal necessitated careful tissue dissection, resulting in the loss of tip support and dorsal irregularity. To restore the tip support and camouflage the dorsum shape, an autologous tissue graft was needed. Conclusion Removal of threads at the tip and dorsum was accompanied by structural weakening and partial tissue loss, which required tip support restoration and dorsum camouflage.
{"title":"Presentation Patterns and Surgical Management of the Complications of Thread Rhinoplasty","authors":"Hong-Ryul Jin, S. Kim","doi":"10.21053/ceo.2022.00101","DOIUrl":"https://doi.org/10.21053/ceo.2022.00101","url":null,"abstract":"Objectives Nonsurgical rhinoplasty using threads has gained popularity in recent years. While the benefits of this procedure have been emphasized, possible complications and their management are not well-known. This study aimed to present the surgical management and results of the complications of thread rhinoplasty. Methods We retrospectively reviewed the medical records of seven patients who underwent revision rhinoplasty due to the complications of thread rhinoplasty from January 2018 to May 2021. The presentation of complications, detailed surgical procedures, and outcomes of revision rhinoplasty were reviewed. Results Visible or extruded threads at the tip were the most common complication, followed by dorsum irregularity. All the threads were unabsorbed and intact in shape, even several years after insertion. Thread removal necessitated careful tissue dissection, resulting in the loss of tip support and dorsal irregularity. To restore the tip support and camouflage the dorsum shape, an autologous tissue graft was needed. Conclusion Removal of threads at the tip and dorsum was accompanied by structural weakening and partial tissue loss, which required tip support restoration and dorsum camouflage.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"247 - 253"},"PeriodicalIF":3.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43403069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Huh, Pilkeun Jang, Seung Hoon Han, R. Mohammad, Woo-Jin Jeong, W. Cha
Objectives. Vocal fold injection (VFI) via the cricothyroid (CT) membrane is used to treat various diseases affecting the vocal folds. The technical challenges of this technique are mainly related to the invisibility of the needle. Real-time light-guided VFI (RL-VFI) was recently developed for injection under simultaneous light guidance in the CT approach. Herein, we present the first clinical trial of RL-VFI, in which we investigated the feasibility and safety of this new technique in unilateral vocal fold paralysis (VFP). Methods. This prospective pilot study enrolled 40 patients, who were treated with RL-VFI for unilateral VFP between September 2020 and August 2021. Adverse events were monitored during the procedure and for 4 weeks postoperatively. The Voice Handicap Index-10, the GRBAS (grade, roughness, breathiness, asthenia, and strain) scale, aerodynamic studies, and acoustic analyses were evaluated to compare the voice improvement after 4 weeks with the baseline values. Results. The needle tip was intuitively identified by the red light. The mean procedure time was 95.6±40.6 seconds for the initial injection, while the additional injection required 79.2±70.5 seconds. The injection was performed under light guidance without additional manipulation after the needle reached the intended point. No acute or delayed adverse events were reported. Among the 40 patients, 36 completed voice analyses after 4 weeks. Subjective and objective voice parameters, including the Voice Handicap Index-10, GRBAS scale, maximum phonation time, mean expiratory airflow, fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio improved significantly after RL-VFI (P<0.05), while the expiratory volume was maintained. Conclusion. RL-VFI is feasible and safe for treating patients with unilateral VFP. This technique is anticipated to improve the precision and safety of the CT approach in the treatment of unilateral VFP. This study provides a rationale for further structured clinical studies.
{"title":"Real-Time Light-Guided Vocal Fold Injection via the Cricothyroid Membrane in Unilateral Vocal Fold Paralysis: A Human Pilot Study","authors":"G. Huh, Pilkeun Jang, Seung Hoon Han, R. Mohammad, Woo-Jin Jeong, W. Cha","doi":"10.21053/ceo.2021.02264","DOIUrl":"https://doi.org/10.21053/ceo.2021.02264","url":null,"abstract":"Objectives. Vocal fold injection (VFI) via the cricothyroid (CT) membrane is used to treat various diseases affecting the vocal folds. The technical challenges of this technique are mainly related to the invisibility of the needle. Real-time light-guided VFI (RL-VFI) was recently developed for injection under simultaneous light guidance in the CT approach. Herein, we present the first clinical trial of RL-VFI, in which we investigated the feasibility and safety of this new technique in unilateral vocal fold paralysis (VFP). Methods. This prospective pilot study enrolled 40 patients, who were treated with RL-VFI for unilateral VFP between September 2020 and August 2021. Adverse events were monitored during the procedure and for 4 weeks postoperatively. The Voice Handicap Index-10, the GRBAS (grade, roughness, breathiness, asthenia, and strain) scale, aerodynamic studies, and acoustic analyses were evaluated to compare the voice improvement after 4 weeks with the baseline values. Results. The needle tip was intuitively identified by the red light. The mean procedure time was 95.6±40.6 seconds for the initial injection, while the additional injection required 79.2±70.5 seconds. The injection was performed under light guidance without additional manipulation after the needle reached the intended point. No acute or delayed adverse events were reported. Among the 40 patients, 36 completed voice analyses after 4 weeks. Subjective and objective voice parameters, including the Voice Handicap Index-10, GRBAS scale, maximum phonation time, mean expiratory airflow, fundamental frequency, jitter, shimmer, and noise-to-harmonics ratio improved significantly after RL-VFI (P<0.05), while the expiratory volume was maintained. Conclusion. RL-VFI is feasible and safe for treating patients with unilateral VFP. This technique is anticipated to improve the precision and safety of the CT approach in the treatment of unilateral VFP. This study provides a rationale for further structured clinical studies.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"264 - 272"},"PeriodicalIF":3.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42332533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives The aim of this study was to evaluate the differences in clinical and laboratory features between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS and to compare diagnostic criteria for ECRS. Methods We compared clinical features and/or laboratory findings classified as ECRS and non-ECRS according to various diagnostic criteria (histological and clinical). We also analyzed studies to compare endoscopic findings, symptom scores, laboratory findings, and computed tomography (CT) findings between ECRS and non-ECRS. Results Our search included 55 studies with 6,143 patients. A comparison of clinical features and/or laboratory criteria with histological criteria showed no significant differences in nasal symptom scores and CT scores according to criteria. Serum eosinophil levels showed differences across the criteria, with ECRS consistently characterized by higher serum eosinophil levels than non-ECRS. Among the four criteria, the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria and tissue eosinophilia (≥70) were associated with decreased olfactory function. In laboratory findings, the eosinophil percentage (standardized mean difference [SMD], 1.561; 95% confidence interval [CI], 1.329–1.794; P<0.001) and eosinophil count (SMD, 1.493; 95% CI, 1.134–1.852; P<0.001) of eosinophils were higher in ECRS than non-ECRS. In clinical findings, nasal symptom scores (SMD, 0.382; 95% CI, 0.156–0.608; P<0.001), endoscopic nasal polyp scores (SMD, 0.581; 95% CI, 0.314–0.848; P<0.001), and olfactory dysfunction (SMD, 0.416; 95% CI, 0.037–0.794; P=0.031) were higher in ECRS than in non-ECRS. With regard to CT findings, the whole-sinus opacification score (SMD, 0.824; 95% CI, 0.588–1.059; P<0.001) was higher in ECRS than in non-ECRS. In particular, there were significant differences in anterior ethmoid sinus and sphenoid sinus opacification. Conclusion ECRS and non-ECRS differ in their clinical and laboratory features. When histological confirmation is difficult on an outpatient basis, ECRS could be diagnosed using clinical features and/or laboratory findings.
{"title":"Clinical and Laboratory Features of Various Criteria of Eosinophilic Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis","authors":"D. Kim, S. Kim, M. Basurrah, S. Hwang","doi":"10.21053/ceo.2022.00052","DOIUrl":"https://doi.org/10.21053/ceo.2022.00052","url":null,"abstract":"Objectives The aim of this study was to evaluate the differences in clinical and laboratory features between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS and to compare diagnostic criteria for ECRS. Methods We compared clinical features and/or laboratory findings classified as ECRS and non-ECRS according to various diagnostic criteria (histological and clinical). We also analyzed studies to compare endoscopic findings, symptom scores, laboratory findings, and computed tomography (CT) findings between ECRS and non-ECRS. Results Our search included 55 studies with 6,143 patients. A comparison of clinical features and/or laboratory criteria with histological criteria showed no significant differences in nasal symptom scores and CT scores according to criteria. Serum eosinophil levels showed differences across the criteria, with ECRS consistently characterized by higher serum eosinophil levels than non-ECRS. Among the four criteria, the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria and tissue eosinophilia (≥70) were associated with decreased olfactory function. In laboratory findings, the eosinophil percentage (standardized mean difference [SMD], 1.561; 95% confidence interval [CI], 1.329–1.794; P<0.001) and eosinophil count (SMD, 1.493; 95% CI, 1.134–1.852; P<0.001) of eosinophils were higher in ECRS than non-ECRS. In clinical findings, nasal symptom scores (SMD, 0.382; 95% CI, 0.156–0.608; P<0.001), endoscopic nasal polyp scores (SMD, 0.581; 95% CI, 0.314–0.848; P<0.001), and olfactory dysfunction (SMD, 0.416; 95% CI, 0.037–0.794; P=0.031) were higher in ECRS than in non-ECRS. With regard to CT findings, the whole-sinus opacification score (SMD, 0.824; 95% CI, 0.588–1.059; P<0.001) was higher in ECRS than in non-ECRS. In particular, there were significant differences in anterior ethmoid sinus and sphenoid sinus opacification. Conclusion ECRS and non-ECRS differ in their clinical and laboratory features. When histological confirmation is difficult on an outpatient basis, ECRS could be diagnosed using clinical features and/or laboratory findings.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"230 - 246"},"PeriodicalIF":3.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49569130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alphonse Umugire, Sungsu Lee, Chang-Joon Lee, Y. Choi, Taekyoung Kim, Hyong-Ho Cho
Objectives Hyaluronan synthase 1 (HAS1) is a membrane-bound protein that is abundant in the epidermis and dermis, and it is important for skin function. However, its association with hearing loss has not yet been studied. Herein, we sought to evaluate the potential contribution of HAS1: c.1082G>A to genetic hearing loss. Methods We used whole-exome sequencing to analyze blood DNA samples of six patients of a family with autosomal dominant familial late-onset progressive hearing loss, which was revealed to be related to a variant of the HAS1 gene. Confirmatory Sanger sequencing was performed with samples from 10 members. A missense variant was detected in HAS1 (c.1082 G>A, p.Cys361Tyr). In silico analyses predicted this variant to result in the functional loss of HAS1. Immunostaining was conducted using wild-type mouse samples to verify HAS1 expression. Results Has1 was detected in an otocyst at E10.5. In the pup, Has1 expression was localized in the stria vascularis (SV), hair cells, supporting cells of the organ of Corti, and some spiral ganglion neurons. SV marginal cells markedly expressed Has1 in the adult stage. The hearing threshold in the Has1-depleted condition was investigated by accessing the International Mouse Phenotyping Consortium’s Auditory Brainstem Response (ABR) data. ABR of Has1 knock-out mice showed threshold elevations at 6, 12, and 18 kHz in young male adults. Conclusion HAS1 may have a close relationship with auditory function and genetic hearing loss. Further investigation is needed to reveal the precise role of HAS1 in the auditory system. HAS1 is a candidate gene for future hereditary hearing loss genetic testing.
透明质酸合成酶1 (Hyaluronan synthase 1, HAS1)是一种富含表皮和真皮层的膜结合蛋白，对皮肤功能具有重要作用。然而，其与听力损失的关系尚未得到研究。在此，我们试图评估HAS1: c.1082G>A对遗传性听力损失的潜在贡献。方法采用全外显子组测序对6例常染色体显性家族性晚发型进行性听力损失患者的血液DNA样本进行分析，发现其与HAS1基因变异有关。对10名成员的样本进行验证性Sanger测序。在HAS1中检测到一个错义变体(c.1082)p.Cys361Tyr G >)。计算机分析预测这种变异会导致HAS1的功能丧失。使用野生型小鼠样本进行免疫染色以验证HAS1的表达。结果在E10.5时耳囊肿中检测到Has1。在幼犬中，Has1的表达定位于血管纹(SV)、毛细胞、Corti器官的支持细胞和部分螺旋神经节神经元。成年期SV边缘细胞明显表达Has1。通过访问国际小鼠表型联盟的听觉脑干反应(ABR)数据，研究了has1缺失条件下的听力阈值。Has1基因敲除小鼠的ABR在年轻雄性成年小鼠中显示6、12和18 kHz的阈值升高。结论HAS1可能与听力功能及遗传性听力损失密切相关。需要进一步的研究来揭示HAS1在听觉系统中的确切作用。HAS1是未来遗传性听力损失基因检测的候选基因。
{"title":"Hyaluronan Synthase 1: A Novel Candidate Gene Associated With Late-Onset Non-syndromic Hereditary Hearing Loss","authors":"Alphonse Umugire, Sungsu Lee, Chang-Joon Lee, Y. Choi, Taekyoung Kim, Hyong-Ho Cho","doi":"10.21053/ceo.2022.00038","DOIUrl":"https://doi.org/10.21053/ceo.2022.00038","url":null,"abstract":"Objectives Hyaluronan synthase 1 (HAS1) is a membrane-bound protein that is abundant in the epidermis and dermis, and it is important for skin function. However, its association with hearing loss has not yet been studied. Herein, we sought to evaluate the potential contribution of HAS1: c.1082G>A to genetic hearing loss. Methods We used whole-exome sequencing to analyze blood DNA samples of six patients of a family with autosomal dominant familial late-onset progressive hearing loss, which was revealed to be related to a variant of the HAS1 gene. Confirmatory Sanger sequencing was performed with samples from 10 members. A missense variant was detected in HAS1 (c.1082 G>A, p.Cys361Tyr). In silico analyses predicted this variant to result in the functional loss of HAS1. Immunostaining was conducted using wild-type mouse samples to verify HAS1 expression. Results Has1 was detected in an otocyst at E10.5. In the pup, Has1 expression was localized in the stria vascularis (SV), hair cells, supporting cells of the organ of Corti, and some spiral ganglion neurons. SV marginal cells markedly expressed Has1 in the adult stage. The hearing threshold in the Has1-depleted condition was investigated by accessing the International Mouse Phenotyping Consortium’s Auditory Brainstem Response (ABR) data. ABR of Has1 knock-out mice showed threshold elevations at 6, 12, and 18 kHz in young male adults. Conclusion HAS1 may have a close relationship with auditory function and genetic hearing loss. Further investigation is needed to reveal the precise role of HAS1 in the auditory system. HAS1 is a candidate gene for future hereditary hearing loss genetic testing.","PeriodicalId":10318,"journal":{"name":"Clinical and Experimental Otorhinolaryngology","volume":"15 1","pages":"220 - 229"},"PeriodicalIF":3.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46628628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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