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Hearing Disorders: HELP
Articles from Miami
Based on 143 articles published since 2010
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These are the 143 published articles about Hearing Disorders that originated from Miami during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Review Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities. 2019

Mittal, Rahul / Pena, Stefanie A / Zhu, Angela / Eshraghi, Nicolas / Fesharaki, Arian / Horesh, Elijah J / Mittal, Jeenu / Eshraghi, Adrien A. ·a Department of Otolaryngology, Hearing Research Laboratory , University of Miami Miller School of Medicine , Miami , FL, USA. · b Department of Neurological Surgery , University of Miami Miller School of Medicine , Miami , FL, USA. ·Artif Cells Nanomed Biotechnol · Pubmed #30987439.

ABSTRACT: Hearing loss is the most common neurosensory impairment worldwide. While conductive hearing loss can be managed by surgery, the management of sensorineural hearing loss (SNHL), related to the damage of sensory cells of the inner ear is more challenging to manage medically. Many causes of SNHL such as sudden idiopathic SNHL, Meniere's disease, noise-induced hearing loss, autoimmune hearing loss or hearing loss from exposure to ototoxic substances can benefit from delivery of otoprotective drugs to the inner ear. However, systemic drug delivery through oral, intravenous and intramuscular methods leads to undesirable side effects due to the inner ear's limited blood supply and the relatively poor penetration of the blood-inner ear barrier (BLB). Therefore, there has been an increased interest for the targeted drug delivery to the inner ear using nanoparticles. Drug delivery through nanoparticles offers several advantages including drug stabilization for controlled release and surface modification for specific targeting. Understanding the biocompatibility of nanoparticles with cochlea and developing novel non-invasive delivery methods will promote the translation of nanoparticle-mediated drug delivery for auditory disorders from bench to bedside.

2 Review A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review. 2019

Li, Taoxi / Feng, Yong / Liu, Yalan / He, Chufeng / Liu, Jing / Chen, Hongsheng / Deng, Yuyuan / Li, Meng / Li, Wu / Song, Jian / Niu, Zhijie / Sang, Shushan / Wen, Jie / Men, Meichao / Chen, Xiaoya / Li, Jiada / Liu, Xuezhong / Ling, Jie. ·Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, Hunan 410008, China; Center for Medical Genetics, Central South University, Changsha, Hunan 410008, China. · Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, Hunan 410008, China; Center for Medical Genetics, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. · Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. · Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, Hunan 410008, China. · Center for Medical Genetics, Central South University, Changsha, Hunan 410008, China. · Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Otolaryngology, University of Miami, Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Institute of Molecular Precision Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: lingjie@sklmg.edu.cn. ·Gene · Pubmed #30974196.

ABSTRACT: Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.

3 Review Role of microRNAs in inner ear development and hearing loss. 2019

Mittal, Rahul / Liu, George / Polineni, Sai P / Bencie, Nicole / Yan, Denise / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: r.mittal11@med.miami.edu. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: xliu@med.miami.edu. ·Gene · Pubmed #30389561.

ABSTRACT: The etiology of hearing loss tends to be multi-factorial and affects a significant proportion of the global population. Despite the differences in etiology, a common physical pathological change that leads to hearing loss is damage to the mechanosensory hair cells of the inner ear. MicroRNAs (miRNAs) have been shown to play a role in inner ear development and thus, may play a role in the development or prevention of hearing loss. In this paper, we review the mechanism of action of miRNAs in the auditory system. We present an overview about the role of miRNAs in inner ear development, summarize the current research on the role of miRNAs in gene regulation, and discuss the effects of both miRNA mutations as well as overexpression. We discuss the crucial role of miRNAs in ensuring normal physiological development of the inner ear. Any deviation from the proper function of miRNA in the cochlea seems to contribute to deleterious damage to the structure of the auditory system and subsequently results in hearing loss. As interest for miRNA research increases, this paper serves as a platform to review current understandings and postulate future avenues for research. A better knowledge about the role of miRNA in the auditory system will help in developing novel treatment modalities for restoring hearing function based on regeneration of damaged inner ear hair cells.

4 Review Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111). 2018

Eshraghi, Adrien A / Aranke, Mayank / Salvi, Richard / Ding, Dalian / Coleman, John K M / Ocak, Emre / Mittal, Rahul / Meyer, Thomas. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: aeshraghi@med.miami.edu. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. · 137 Cary Hall, Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA; Department of Audiology and Speech-Language Pathology, Asia University, Taichung, Taiwan. · 137 Cary Hall, Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, USA. · JohnCo Research, 3109 Mount Carol Drive, San Diego, CA, USA. · Auris Medical AG, Basel, Switzerland. ·Hear Res · Pubmed #29573879.

ABSTRACT: There is a growing interest in the auditory community to develop novel prophylactic and therapeutic drugs to prevent permanent sensorineural hearing loss following acute cochlear injury. The jun-N-terminal protein kinase (JNK) pathway plays a crucial role in acute sensory hearing loss. Blocking the JNK pathway using the cell-penetrating peptide D-JNKI-1 (AM-111/brimapitide) has shown promise as both a prophylactic and therapeutic agent for acute cochlear injury. A number of pre-clinical and clinical studies have determined the impact of D-JNKI-1 on acute sensorineural hearing loss. Given the inner-ear selective therapeutic profile, local route of administration, and ability to diffuse across cellular membranes rapidly using both active and passive transport makes D-JNK-1 a promising oto-protective drug. In this review article, we discuss the application of D-JNKI-1 in various auditory disorders as well as its pharmacological properties and distribution in the cochlea.

5 Review Advanced Otosclerosis: Stapes Surgery or Cochlear Implantation? 2018

Eshraghi, Adrien A / Ila, Kadri / Ocak, Emre / Telischi, Fred F. ·Department of Otolaryngology, University of Miami Miller School of Medicine, 1600 Northwest 10th Avenue, Miami, FL 33136, USA. Electronic address: aeshraghi@med.miami.edu. · Department of Otolaryngology, University of Miami Miller School of Medicine, 1600 Northwest 10th Avenue, Miami, FL 33136, USA. ·Otolaryngol Clin North Am · Pubmed #29502727.

ABSTRACT: Diagnosis and treatment of advanced otosclerosis can be controversial. In 1961, House and Sheehy defined advanced otosclerosis as hearing loss in air conduction threshold by 85 dB with nonmeasurable bone conduction. Recently, the definition of advanced otosclerosis is mostly based on the decrease of speech recognition. There are some treatment modalities: stapes surgery and hearing aids, cochlear implantation, or direct acoustic cochlear implant. The authors propose a new algorithm for treatment. If the patient is treated with cochlear implantation, the surgeon should be cautious for facial nerve stimulation after surgery because it is the most prevalent complication.

6 Review Impact of Imaging in Management of Otosclerosis. 2018

Wolfovitz, Amit / Luntz, Michal. ·Department of Otolaryngology-Head and Neck Surgery, University of Miami, Miller School of Medicine, 1120 N.W. 14th Street, #5, Miami, FL 33136, USA. · Department of Otolaryngology-Head and Neck Surgery, Bnai Zion Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israeli School of Technology, Golomb 47 Street, Haifa 31048, Israel. Electronic address: michal.luntz@b-zion.org.il. ·Otolaryngol Clin North Am · Pubmed #29502724.

ABSTRACT: The use of imaging in otosclerosis for diagnosis, preoperative assessment, and follow-up has the potential to give the clinician an additional tier of patient evaluation and validation of diagnosis. Before stapes surgery, imaging may help avoid unnecessary middle ear explorations in nonotosclerotic cases, prevent potential complications, and assist in appropriate patient counseling regarding management expectations. Postoperatively, following unsuccessful air-bone gap closure in stapes surgery or conductive hearing deterioration following initial successful closure of the air bone gap, imaging can be used to determine the prosthesis position in the middle ear.

7 Review Precision medicine in hearing loss. 2018

Rudman, Jason R / Mei, Christine / Bressler, Sara E / Blanton, Susan H / Liu, Xue-Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: x.liu1@med.miami.edu. ·J Genet Genomics · Pubmed #29500086.

ABSTRACT: Precision medicine (PM) proposes customized medical care based on a patient's unique genome, biomarkers, environment and behaviors. Hearing loss (HL) is the most common sensorineural disorder worldwide and is frequently caused by a single genetic mutation. With recent advances in PM tools such as genetic sequencing and data analysis, the field of HL is ideally positioned to adopt the strategies of PM. Here, we review current and future applications of PM in HL as they relate to the four core qualities of PM (P4): predictive, personalized, patient-centered, and participatory. We then introduce a strategy for effective incorporation of HL PM into the design of future research studies, electronic medical records, and clinical practice to improve diagnostics, prognostics, and, ultimately, individualized patient treatment. Finally, specific anticipated ethical and economic concerns in this growing era of genomics-based HL treatment are discussed. By integrating PM principles into translational HL research and clinical practice, hearing specialists are uniquely positioned to effectively treat the heterogeneous causes and manifestations of HL on an individualized basis.

8 Review Genetic basis of hearing loss in Spanish, Hispanic and Latino populations. 2018

Mittal, Rahul / Patel, Amit P / Nguyen, Desiree / Pan, Debbie R / Jhaveri, Vasanti M / Rudman, Jason R / Dharmaraja, Arjuna / Yan, Denise / Feng, Yong / Chapagain, Prem / Lee, David J / Blanton, Susan H / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China. · Department of Physics and Biomolecular Sciences Institute, Florida International University, Miami, FL, USA. · Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China; Tsinghua University School of Medicine, Beijing 10084, China; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: xliu@med.miami.edu. ·Gene · Pubmed #29331482.

ABSTRACT: Hearing loss (HL) is the most common neurosensory disorder affecting humans. The screening, prevention and treatment of HL require a better understanding of the underlying molecular mechanisms. Genetic predisposition is one of the most common factors that leads to HL. Most HL studies include few Spanish, Hispanic and Latino participants, leaving a critical gap in our understanding about the prevalence, impact, unmet health care needs, and genetic factors associated with hearing impairment among Spanish, Hispanic and Latino populations. The few studies which have been performed show that the gene variants commonly associated with HL in non-Spanish and non-Hispanic populations are infrequently responsible for hearing impairment in Spanish as well as Hispanic and Latino populations (hereafter referred to as Hispanic). To design effective screening tools to detect HL in Spanish and Hispanic populations, studies must be conducted to determine the gene variants that are most commonly associated with hearing impairment in this racial/ethnic group. In this review article, we summarize gene variants and loci associated with HL in Spanish and Hispanic populations. Identifying new genetic variants associated with HL in Spanish and Hispanic populations will pave the way to develop effective screening tools and therapeutic strategies for HL.

9 Review The genetic basis of deafness in populations of African descent. 2017

Rudman, Jason R / Kabahuma, Rosemary I / Bressler, Sara E / Feng, Yong / Blanton, Susan H / Yan, Denise / Liu, Xue-Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otorhinolaryngology, Steve Biko Academic Hospital, University of Pretoria, Pretoria 0001, South Africa. Electronic address: kabahumar2@gmail.com. · Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410008, China. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410008, China; Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: x.liu1@med.miami.edu. ·J Genet Genomics · Pubmed #28642064.

ABSTRACT: Hearing loss is the most common sensorineural disorder worldwide and is associated with more than 1000 mutations in more than 90 genes. While mutations in genes such as GJB2 (gap-junction protein β 2) and GJB6 (gap-junction protein β 6) are highly prevalent in Caucasian, Asian, and Middle Eastern populations, they are rare in both native African populations and those of African descent. The objective of this paper is to review the current knowledge regarding the epidemiology and genetics of hearing loss in African populations with a focus on native sub-Saharan African populations. Environmental etiologies related to poor access to healthcare and perinatal care account for the majority of cases. Syndromic etiologies including Waardenburg, Pendred and Usher syndromes are uncommon causes of hearing loss in these populations. Of the non-syndromic causes, common mutations in GJB2 and GJB6 are rarely implicated in populations of African descent. Recent use of next-generation sequencing (NGS) has identified several candidate deafness genes in African populations from Nigeria and South Africa that are unique when compared to common causative mutations worldwide. Researchers also recently described a dominant mutation in MYO3a in an African American family with non-syndromic hearing loss. The use of NGS and specialized panels will aid in identifying rare and novel mutations in a more cost- and time-effective manner. The identification of common hearing loss mutations in indigenous African populations will pave the way for translation into genetic deafness research in populations of African descent worldwide.

10 Review The Advances in Hearing Rehabilitation and Cochlear Implants in China. 2017

Li, Jia-Nan / Chen, Si / Zhai, Lei / Han, Dong-Yi / Eshraghi, Adrien A / Feng, Yong / Yang, Shi-Ming / Liu, Xue-Zhong. ·1Department of Otolaryngology & Head and Neck Surgery, and Auditory Implantation Center, Chinese PLA General Hospital, Beijing, People's Republic of China; 2Department of Otolaryngology, University of Miami Ear Institute, Miami, Florida, USA; 3China Rehabilitation Research Center for Deaf Children, Beijing, People's Republic of China; 4Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; and 5Tsinghua University School of Medicine, Beijing, People's Republic of China. ·Ear Hear · Pubmed #28471842.

ABSTRACT: Hearing loss (HL) is a common sensory impairment in humans, with significant economic and social impacts. With nearly 20% of the world's population, China has focused on economic development and health awareness to improve the care for its hearing-impaired population. Recently, the Chinese government has initiated national programs such as the China Disabled Persons Federation to fund prevention, treatment, and rehabilitation of hearing impairment. Newborn hearing screening and auditory rehabilitation programs in China have expanded exponentially with government support. While facing many challenges and overcoming obstacles, cochlear implantation (CI) programs in China have also experienced considerable growth. This review discusses the implementation of CI programs for HL in China and presents current HL data including epidemiology, newborn hearing screening, and determination of genetic etiologies. Sharing the experience in Chinese auditory rehabilitation and CI programs will shine a light on the developmental pathway of healthcare infrastructure to meet emerging needs of the hearing-impaired population in other developing countries.

11 Review The Genomic Basis of Noise-induced Hearing Loss: A Literature Review Organized by Cellular Pathways. 2016

Clifford, Royce Ellen / Hoffer, Michael / Rogers, Rick. ·*Veteran's Administration Hospitals, La Jolla, California and Harvard School of Public Health, Boston, Massachusetts †Miami University, Oxford, Ohio. ·Otol Neurotol · Pubmed #27518140.

ABSTRACT: OBJECTIVE: Using Reactome, a curated Internet database, noise-induced hearing loss studies were aggregated into cellular pathways for organization of the emerging genomic and epigenetic data in the literature. DATA SOURCES: PubMed and Reactome.org, a relational data base program systematizing biological processes into interactive pathways and subpathways based on ontology, cellular constituents, gene expression, and molecular components. STUDY SELECTION: Peer-reviewed population and laboratory studies for the previous 15 years relating genomics and noise and hearing loss were identified in PubMed. Criteria included p values <0.05 with correction for multiple genes, a fold change of >1.5, or duplicated studies. DATA EXTRACTION AND SYNTHESIS: One-hundred fifty-eight unique HGNC identifiers from 77 articles met the selection criteria, and were uploaded into the analysis program at http://reactome.org. These genes participated in a total of 621 cellular interactions in 21 of 23 pathways. Cellular response to stress with its attenuation phase, particularly in response to heat stress, detoxification of ROS, and specific areas of the immune system are predominant pathways identified as significantly 'overrepresented' (p values <0.1e-5 and false discovery rates <0.01). CONCLUSION: Twenty-one of 23 of the designated pathways in Reactome have significant influence on noise-induced hearing loss, signifying a confluence of molecular pathways in reaction to acoustic trauma; however, cellular response to stress, including heat shock response, and other small areas of immune response were highly overrepresented. Yet-to-be-explored genomics areas include miRNA, lncRNA, copy number variations, RNA sequencing, and human genome-wide association study.

12 Review Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System. 2016

Mittal, Rahul / Chan, Brandon / Grati, M'hamed / Mittal, Jeenu / Patel, Kunal / Debs, Luca H / Patel, Amit P / Yan, Denise / Chapagain, Prem / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida. · Department of Physics, Florida International University, Miami, Florida. · Biomolecular Science Institute, Florida International University, Miami, Florida. · Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida. · Department of Biochemistry, University of Miami Miller School of Medicine, Miami, Florida. ·J Cell Physiol · Pubmed #26627116.

ABSTRACT: The P2X purinergic receptors are cation-selective channels gated by extracellular adenosine 5'-triphosphate (ATP). These purinergic receptors are found in virtually all mammalian cell types and facilitate a number of important physiological processes. Within the past few years, the characterization of crystal structures of the zebrafish P2X4 receptor in its closed and open states has provided critical insights into the mechanisms of ligand binding and channel activation. Understanding of this gating mechanism has facilitated to design and interpret new modeling and structure-function experiments to better elucidate how different agonists and antagonists can affect the receptor with differing levels of potency. This review summarizes the current knowledge on the structure, activation, allosteric modulators, function, and location of the different P2X receptors. Moreover, an emphasis on the P2X2 receptors has been placed in respect to its role in the auditory system. In particular, the discovery of three missense mutations in P2X2 receptors could become important areas of study in the field of gene therapy to treat progressive and noise-induced hearing loss. J. Cell. Physiol. 231: 1656-1670, 2016. © 2015 Wiley Periodicals, Inc.

13 Review The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations. 2015

Yan, Denise / Kannan-Sundhari, Abhiraami / Vishwanath, Subramanian / Qing, Jie / Mittal, Rahul / Kameswaran, Mohan / Liu, Xue Zhong. ·1 Departments of Otolaryngology-Head and Neck Surgery, Leonard M. Miller School of Medicine, University of Miami , Miami, Florida. · 2 SRM University , SRM Nagar, Chennai, India . · 3 Madras ENT Research Foundation (MERF) Chennai, India . ·Genet Test Mol Biomarkers · Pubmed #26186295.

ABSTRACT: Deafness encompasses a series of etiologically heterogeneous disorders with mutations in more than 400 independent genes. However, several studies indicate that a large proportion of both syndromic and nonsyndromic forms of deafness in the racially diverse Indian and Pakistani populations are caused by defects in just a few genes. In these countries, there is a strong cultural preference for consanguineous marriage and an associated relatively high prevalence of genetic disorders. The current Indian population is approximately 1.2 billion and it is estimated that 30,000 infants are born with congenital sensorineural hearing loss (HL) each year. The estimated rate of profound bilateral HL is 1.6 per 1000 in Pakistan and 70% of this HL arises in consanguineous families. Knowledge of the genetic cause of deafness within a distinct population is important for accurate genetic counseling and early diagnosis for timely intervention and treatment options. Many sources and technologies are now available for the testing of hearing efficiency. Population-based screening has been proposed as one of the major strategies for translating genetic and genomic advances into population health gains. This review of the genetics of deafness in Indian and Pakistani populations deals with the major causes of deafness in these countries and prospectives for reducing the incidence of inherited deafness.

14 Review Association of PRPS1 Mutations with Disease Phenotypes. 2015

Mittal, Rahul / Patel, Kunal / Mittal, Jeenu / Chan, Brandon / Yan, Denise / Grati, M'hamed / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA ; Department of Biochemistry, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ·Dis Markers · Pubmed #26089585.

ABSTRACT: Phosphoribosylpyrophosphate synthetase 1 (PRPS1) codes for PRS-I enzyme that catalyzes the first step of nucleotide synthesis. PRPS1 gene mutations have been implicated in a number of human diseases. Recently, new mutations in PRPS1 have been identified that have been associated with novel phenotypes like diabetes insipidus expanding the spectrum of PRPS1-related diseases. The purpose of this review is to evaluate current literature on PRPS1-related syndromes and summarize potential therapies. The overexpression of PRPS1 results in PRS-I superactivity resulting in purine overproduction. Patients with PRS-I superactivity demonstrate uric acid overproduction, hypotonia, ataxia, neurodevelopment abnormalities, and postlingual hearing impairment. On the other hand, decreased activity leads to X-linked nonsyndromic sensorineural deafness (DFNX-2), Charcot-Marie-Tooth disease-5 (CMTX5), and Arts syndrome depending on the residual activity of PRS-I. Mild PRS-I deficiency (DFNX-2) results in non-syndromic progressive hearing loss whereas moderate PRS-I deficiency (CMTX5) and severe PRS-I deficiency (Arts syndrome) present with peripheral or optic neuropathy, prelingual progressive sensorineural hearing loss, and central nervous system impairment. Currently, purine replacement via S-adenosylmethionine (SAM) supplementation in patients with Arts syndrome appears to improve their condition. This suggests that SAM supplementation can alleviate symptoms of PRPS1 deficient patients and open new avenues of therapeutic intervention.

15 Review The application of genome editing in studying hearing loss. 2015

Zou, Bing / Mittal, Rahul / Grati, M'hamed / Lu, Zhongmin / Shu, Yilai / Tao, Yong / Feng, Youg / Xie, Dinghua / Kong, Weijia / Yang, Shiming / Chen, Zheng-Yi / Liu, Xuezhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. · Department of Biology, University of Miami, Miami, FL 33146, USA. · Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA; Department of Otology and Skull Base Surgery, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, China. · Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA; Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China. · Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital Central South University, Changsha, Hunan, China. · Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China. · Department of Otology and Laryngology, Harvard Medical School and Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston 02114, USA. Electronic address: zheng-yi_chen@meei.harvard.edu. · Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China; Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital Central South University, Changsha, Hunan, China; Department of Otolaryngology-Head and Neck Surgery, Chinese PLA General Hospital, Beijing, China. Electronic address: xliu@med.miami.edu. ·Hear Res · Pubmed #25987504.

ABSTRACT: Targeted genome editing mediated by clustered, regularly interspaced, short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) technology has emerged as one of the most powerful tools to study gene functions, and with potential to treat genetic disorders. Hearing loss is one of the most common sensory disorders, affecting approximately 1 in 500 newborns with no treatment. Mutations of inner ear genes contribute to the largest portion of genetic deafness. The simplicity and robustness of CRISPR/Cas9-directed genome editing in human cells and model organisms such as zebrafish, mice and primates make it a promising technology in hearing research. With CRISPR/Cas9 technology, functions of inner ear genes can be studied efficiently by the disruption of normal gene alleles through non-homologous-end-joining (NHEJ) mechanism. For genetic hearing loss, CRISPR/Cas9 has potential to repair gene mutations by homology-directed-repair (HDR) or to disrupt dominant mutations by NHEJ, which could restore hearing. Our recent work has shown CRISPR/Cas9-mediated genome editing can be efficiently performed in the mammalian inner ear in vivo. Thus, application of CRISPR/Cas9 in hearing research will open up new avenues for understanding the pathology of genetic hearing loss and provide new routes in the development of treatment to restore hearing. In this review, we describe major methodologies currently used for genome editing. We will highlight applications of these technologies in studies of genetic disorders and discuss issues pertaining to applications of CRISPR/Cas9 in auditory systems implicated in genetic hearing loss.

16 Review Whole-exome sequencing and its impact in hereditary hearing loss. 2015

Atik, Tahir / Bademci, Guney / Diaz-Horta, Oscar / Blanton, Susan H / Tekin, Mustafa. ·Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics,Miller School of Medicine,University of Miami,USA. ·Genet Res (Camb) · Pubmed #25825321.

ABSTRACT: Next-generation sequencing (NGS) technologies have played a central role in the genetic revolution. These technologies, especially whole-exome sequencing, have become the primary tool of geneticists to identify the causative DNA variants in Mendelian disorders, including hereditary deafness. Current research estimates that 1% of all human genes have a function in hearing. To date, mutations in over 80 genes have been reported to cause nonsyndromic hearing loss (NSHL). Strikingly, more than a quarter of all known genes related to NSHL were discovered in the past 5 years via NGS technologies. In this article, we review recent developments in the usage of NGS for hereditary deafness, with an emphasis on whole-exome sequencing.

17 Review Next-generation sequencing in genetic hearing loss. 2013

Yan, Denise / Tekin, Mustafa / Blanton, Susan H / Liu, Xue Zhong. ·Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. ·Genet Test Mol Biomarkers · Pubmed #23738631.

ABSTRACT: The advent of the $1000 genome has the potential to revolutionize the identification of genes and their mutations underlying genetic disorders. This is especially true for extremely heterogeneous Mendelian conditions such as deafness, where the mutation, and indeed the gene, may be private. The recent technological advances in target-enrichment methods and next generation sequencing offer a unique opportunity to break through the barriers of limitations imposed by gene arrays. These approaches now allow for the complete analysis of all known deafness-causing genes and will result in a new wave of discoveries of the remaining genes for Mendelian disorders. In this review, we describe commonly used genomic technologies as well as the application of these technologies to the genetic diagnosis of hearing loss (HL) and to the discovery of novel genes for syndromic and nonsyndromic HL.

18 Review Hearing loss and PRPS1 mutations: Wide spectrum of phenotypes and potential therapy. 2013

Liu, Xue Zhong / Xie, Dinghua / Yuan, Hui Jun / de Brouwer, Arjan P M / Christodoulou, John / Yan, Denise. ·Department of Otolaryngology, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA. xliu@med.Miami.edu ·Int J Audiol · Pubmed #23190330.

ABSTRACT: OBJECTIVE: The purpose of this review was to evaluate the current literature on phosphoribosylpyrophosphate synthetase 1 (PRPS1)-related diseases and their consequences on hearing function. DESIGN: A literature search of peer-reviewed, published journal articles was conducted in online bibliographic databases. STUDY SAMPLE: Three databases for medical research were included in this review. RESULTS: Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss. Hearing loss in male patients with PRPS1 mutations is bilateral, moderate to profound, and can be prelingual or postlingual, progressive or non-progressive. Audiogram shapes associated with PRPS1 deafness are usually residual and flat. Female carriers can have unilateral or bilateral hearing impairment. Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5). CONCLUSIONS: Lower residual activity in PRS-I leads to a more severe clinical manifestation. Clinical and molecular findings suggest that the four PRPS1 disorders discovered to date belong to the same disease spectrum. Dietary supplementation with S-adenosylmethionine (SAM) appeared to alleviate the symptoms of Arts syndrome patients, suggesting that SAM could compensate for PRS-I deficiency.

19 Review Historical Aspects of Inner Ear Anatomy and Biology that Underlie the Design of Hearing and Balance Prosthetic Devices. 2012

Van De Water, Thomas R. ·Cochlear Implant Research Program, University of Miami Ear Institute, Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida 33136-1015, USA. tvandewater@med.miami.edu ·Anat Rec (Hoboken) · Pubmed #23045252.

ABSTRACT: This review presents some of the major historical events that advanced the body of knowledge of the anatomy of the inner ear and its sensory receptors as well as the biology of these receptors that underlies the sensory functions of hearing and balance. This knowledge base of the inner ear's structure/function has been an essential factor for the design and construction of prosthetic devices to aid patients with deficits in their senses of hearing and balance. Prosthetic devices are now available for severely hearing impaired and deaf patients to restore hearing and are known as cochlear implants and auditory brain stem implants. A prosthetic device for patients with balance disorders is being perfected and is in an animal model testing phase with another prosthetic device for controlling intractable dizziness in Meniere's patients currently being evaluated in clinical testing. None of this would have been possible without the pioneering studies and discoveries of the investigators mentioned in this review and with the work of many other talented investigators to numerous to be covered in this review.

20 Review Conservation of hearing and protection of hair cells in cochlear implant patients' with residual hearing. 2012

Bas, Esperanza / Dinh, Christine T / Garnham, Carolyn / Polak, Marek / Van de Water, Thomas R. ·Cochlear Implant Research Program, University of Miami Ear Institute, Miami, Florida 33136-1015, USA. ·Anat Rec (Hoboken) · Pubmed #23044907.

ABSTRACT: This review covers the molecular mechanisms involved in hair cell and hearing losses which can result from trauma generated during the process of cochlear implantation and the contributions of both the intrinsic and extrinsic cell death signaling pathways in producing these trauma/inflammation induced losses. Application of soft surgical techniques to conserve hearing and protect auditory sensory cells during the process of cochlear implantation surgery and insertion of the electrode array during the process of cochlear implantation are reviewed and discussed. The role of drug therapy and mode of drug delivery for the conservation of a cochlear implant patient's residual hearing is presented and discussed.

21 Review Biomedical engineering principles of modern cochlear implants and recent surgical innovations. 2012

Eshraghi, Adrien A / Gupta, Chhavi / Ozdamar, Ozcan / Balkany, Thomas J / Truy, Eric / Nazarian, Ronen. ·Department of Otolaryngology, University of Miami Miller School of Medicine, University of Miami Ear Institute, Miami, Florida 33136-1015, USA. aeshraghi@med.miami.edu ·Anat Rec (Hoboken) · Pubmed #23044779.

ABSTRACT: This review covers the most recent clinical and surgical advances made in the development and application of cochlear implants (CIs). In recent years, dramatic progress has been made in both clinical and basic science aspect of cochlear implantation. Today's modern CI uses multi-channel electrodes with highly miniaturized powerful digital processing chips. This review article describes the function of various components of the modern multi-channel CIs. A selection of the most recent clinical and surgical innovations is presented. This includes the preliminary results with electro-acoustic stimulation or hybrid devices and ongoing basic science research that is focused on the preservation of residual hearing post-implantation. The result of an original device that uses a binaural stimulation mode with a single implanted receiver/stimulator is also presented. The benefit and surgical design of a temporalis pocket technique for the implant's receiver stimulator is discussed. Advances in biomedical engineering and surgical innovations that lead to an increasingly favorable clinical outcome and to an expansion of the indication of CI surgery are presented and discussed.

22 Review The cochlear implant: historical aspects and future prospects. 2012

Eshraghi, Adrien A / Nazarian, Ronen / Telischi, Fred F / Rajguru, Suhrud M / Truy, Eric / Gupta, Chhavi. ·Department of Otolaryngology, University of Miami Ear Institute, University of Miami Miller School of Medicine, Miami, Florida 33136-1015, USA. aeshraghi@med.miami.edu ·Anat Rec (Hoboken) · Pubmed #23044644.

ABSTRACT: The cochlear implant (CI) is the first effective treatment for deafness and severe losses in hearing. As such, the CI is now widely regarded as one of the great advances in modern medicine. This article reviews the key events and discoveries that led up to the current CI systems, and we review and present some among the many possibilities for further improvements in device design and performance. The past achievements include: (1) development of reliable devices that can be used over the lifetime of a patient; (2) development of arrays of implanted electrodes that can stimulate more than one site in the cochlea; and (3) progressive and large improvements in sound processing strategies for CIs. In addition, cooperation between research organizations and companies greatly accelerated the widespread availability and use of safe and effective devices. Possibilities for the future include: (1) use of otoprotective drugs; (2) further improvements in electrode designs and placements; (3) further improvements in sound processing strategies; (4) use of stem cells to replace lost sensory hair cells and neural structures in the cochlea; (5) gene therapy; (6) further reductions in the trauma caused by insertions of electrodes and other manipulations during implant surgeries; and (7) optical rather electrical stimulation of the auditory nerve. Each of these possibilities is the subject of active research. Although great progress has been made to date in the development of the CI, including the first substantial restoration of a human sense, much more progress seems likely and certainly would not be a surprise.

23 Review Genetics of hearing and deafness. 2012

Angeli, Simon / Lin, Xi / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami, Miami, Florida 33136, USA. ·Anat Rec (Hoboken) · Pubmed #23044516.

ABSTRACT: This article is a review of the genes and genetic disorders that affect hearing in humans and a few selected mouse models of deafness. Genetics is playing an increasingly critical role in the practice of medicine. This is not only in part to the importance that genetic knowledge has on traditional genetic diseases but also in part to the fact that genetic knowledge provides an understanding of the fundamental biological process of most diseases. The proteins coded by the genes related to hearing loss (HL) are involved in many functions in the ear, such as cochlear fluid homeostasis, ionic channels, stereocilia morphology and function, synaptic transmission, gene regulation, and others. Mouse models play a crucial role in understanding of the pathogenesis associated with these genes. Different types of familial HL have been recognized for years; however, in the last two decades, there has been tremendous progress in the discovery of gene mutations that cause deafness. Most of the cases of genetic deafness recognized today are monogenic disorders that can be broadly classified by the mode of inheritance (i.e., autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance) and by the presence of associated phenotypic features (i.e., syndromic; and nonsyndromic). In terms of nonsyndromic HL, the chromosomal locations are currently known for ∼ 125 loci (54 for dominant and 71 for recessive deafness), 64 genes have been identified (24 for dominant and 40 for recessive deafness), and there are many more loci for syndromic deafness and X-linked and mitochondrial DNA disorders (http://hereditaryhearingloss.org). Thus, today's clinician must understand the science of medical genetics as this knowledge can lead to more effective disease diagnosis, counseling, treatment, and prevention.

24 Review Habilitation of auditory and vestibular dysfunction. 2012

Snapp, Hillary A / Schubert, Michael C. ·Department of Otolaryngology, University of Miami, 1120 Northwest 14th Street, Fifth Floor, Miami, FL 33136, USA. ·Otolaryngol Clin North Am · Pubmed #22483829.

ABSTRACT: Although unilateral hearing loss is often the initial sign of vestibular schwannoma (VS), the pathogenesis of the associated structures within the cerebellopontine angle can result in vestibular, facial, or vascular symptoms. Removal of a VS causes deficits in hearing, balance, and gaze stability. The resulting hearing loss eliminates the benefits of binaural listening that provide localization, loudness summation, and listening-in-noise ability. Reduced balance and gaze stability increase fall risk. This review discusses modern treatment options for auditory and vestibular rehabilitation including contralateral routing of signals (CROS), bilateral CROS, bone-anchored implants, tinnitus management, gaze and gait stability exercises.

25 Review Cochlear implantation in common forms of genetic deafness. 2010

Vivero, Richard J / Fan, Kenneth / Angeli, Simon / Balkany, Thomas J / Liu, Xue Z. ·Department of Otolaryngology, University of Miami Ear Institute, Miami, FL 33136, United States. ·Int J Pediatr Otorhinolaryngol · Pubmed #20655117.

ABSTRACT: Genetic factors are among the main etiologies of severe to profound hearing loss and may play an important role in cochlear implantation (CI) outcomes. While genes for common forms of deafness have been cloned, efforts to correlate the functional outcome of CIs with a genetic form of deafness carried by the patient have been largely anecdotal to date. It has been suggested that the differences in auditory performance may be explained by differences in the number of surviving spiral ganglion cells, etiology of hearing loss, and other factors. Knowledge of the specific loci and mutations involved in patients who receive cochlear implants may elucidate other factors related to CI performance. In this review article, current knowledge of cochlear implants for hereditary hearing loss will be discussed with an emphasis on relevant clinical genotype-phenotype correlations.

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