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Hearing Disorders: HELP
Articles by Todd E. Scheetz
Based on 9 articles published since 2010
(Why 9 articles?)
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Between 2010 and 2020, Todd E. Scheetz wrote the following 9 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article LADD syndrome with glaucoma is caused by a novel gene. 2017

Simpson, Allie / Avdic, Armin / Roos, Ben R / DeLuca, Adam / Miller, Kathy / Schnieders, Michael J / Scheetz, Todd E / Alward, Wallace L M / Fingert, John H. ·Department of Ophthalmology, Carver College of Medicine, University of Iowa, Iowa City, IA; Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IA. · Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA. · Stephen A. Wynn Institute for Vision Research, University of Iowa, Iowa City, IA; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA. ·Mol Vis · Pubmed #28400699.

ABSTRACT: PURPOSE: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder displaying variable expression of multiple congenital anomalies including hypoplasia or aplasia of the lacrimal and salivary systems causing abnormal tearing and dry mouth. Mutations in the METHODS: Whole exome sequencing was performed, and previously described disease-causing genes ( RESULTS: No mutations were detected in CONCLUSIONS: We report a patient with no mutations in known LADD syndrome genes (

2 Article Audioprofile Surfaces: The 21st Century Audiogram. 2016

Taylor, Kyle R / Booth, Kevin T / Azaiez, Hela / Sloan, Christina M / Kolbe, Diana L / Glanz, Emily N / Shearer, A Eliot / DeLuca, Adam P / Anand, V Nikhil / Hildebrand, Michael S / Simpson, Allen C / Eppsteiner, Robert W / Scheetz, Todd E / Braun, Terry A / Huygen, Patrick L M / Smith, Richard J H / Casavant, Thomas L. ·Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa, USA Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, Iowa, USA. · Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA. · Department of Molecular Physiology and Biophysics, University of Iowa Carver, Iowa City, Iowa, USA. · Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA. · Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, Iowa, USA. · Department of Electrical and Computer Engineering, University of Iowa, Iowa City, Iowa, USA Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, Iowa, USA Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, USA. · Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. · Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA Department of Molecular Physiology and Biophysics, University of Iowa Carver, Iowa City, Iowa, USA richard-smith@uiowa.edu. ·Ann Otol Rhinol Laryngol · Pubmed #26530094.

ABSTRACT: OBJECTIVE: To present audiometric data in 3 dimensions by considering age as an addition dimension. METHODS: Audioprofile surfaces (APSs) were fitted to a set of audiograms by plotting each measurement of an audiogram as an independent point in 3 dimensions with the x, y, and z axes representing frequency, hearing loss in dB, and age, respectively. RESULTS: Using the Java-based APS viewer as a standalone application, APSs were pre-computed for 34 loci. By selecting APSs for the appropriate genetic locus, a clinician can compare this APS-generated average surface to a specific patient's audiogram. CONCLUSION: Audioprofile surfaces provide an easily interpreted visual representation of a person's hearing acuity relative to others with the same genetic cause of hearing loss. Audioprofile surfaces will support the generation and testing of sophisticated hypotheses to further refine our understanding of the biology of hearing.

3 Article Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. 2014

Shearer, A Eliot / Eppsteiner, Robert W / Booth, Kevin T / Ephraim, Sean S / Gurrola, José / Simpson, Allen / Black-Ziegelbein, E Ann / Joshi, Swati / Ravi, Harini / Giuffre, Angelica C / Happe, Scott / Hildebrand, Michael S / Azaiez, Hela / Bayazit, Yildirim A / Erdal, Mehmet Emin / Lopez-Escamez, Jose A / Gazquez, Irene / Tamayo, Marta L / Gelvez, Nancy Y / Leal, Greizy Lopez / Jalas, Chaim / Ekstein, Josef / Yang, Tao / Usami, Shin-ichi / Kahrizi, Kimia / Bazazzadegan, Niloofar / Najmabadi, Hossein / Scheetz, Todd E / Braun, Terry A / Casavant, Thomas L / LeProust, Emily M / Smith, Richard J H. ·Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. · Agilent Technologies, Cedar Creek, TX 78612, USA. · Epilepsy Research Centre, Department of Medicine, University of Melbourne, Heidelberg, VIC 3084, Australia. · Department of Otolaryngology, Faculty of Medicine, Medipol University, Istanbul 34083, Turkey. · Department of Medical Biology and Genetics, University of Mersin, Mersin 33160, Turkey. · Otology and Neurotology Group CTS495, Center for Genomic and Oncological Research (GENyO), Granada 18012, Spain. · Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá 11001000, Colombia. · Bonei Olam, Center for Rare Jewish Genetic Disorders, Brooklyn, NY 11204, USA. · Dor Yeshorim, The Committee for Prevention of Jewish Genetic Diseases, Brooklyn, NY 11211, USA. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, and the Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 20025, China. · Department of Otorhinolaryngology, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. · Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA; Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, IA 52242, USA; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA. · Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: richard-smith@uiowa.edu. ·Am J Hum Genet · Pubmed #25262649.

ABSTRACT: Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

4 Article Advancing genetic testing for deafness with genomic technology. 2013

Shearer, A Eliot / Black-Ziegelbein, E Ann / Hildebrand, Michael S / Eppsteiner, Robert W / Ravi, Harini / Joshi, Swati / Guiffre, Angelica C / Sloan, Christina M / Happe, Scott / Howard, Susanna D / Novak, Barbara / Deluca, Adam P / Taylor, Kyle R / Scheetz, Todd E / Braun, Terry A / Casavant, Thomas L / Kimberling, William J / Leproust, Emily M / Smith, Richard J H. ·Department of Otolaryngology-Head and Neck Surgery, Molecular Otolaryngology & Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA. ·J Med Genet · Pubmed #23804846.

ABSTRACT: BACKGROUND: Non-syndromic hearing loss (NSHL) is the most common sensory impairment in humans. Until recently its extreme genetic heterogeneity precluded comprehensive genetic testing. Using a platform that couples targeted genomic enrichment (TGE) and massively parallel sequencing (MPS) to sequence all exons of all genes implicated in NSHL, we tested 100 persons with presumed genetic NSHL and in so doing established sequencing requirements for maximum sensitivity and defined MPS quality score metrics that obviate Sanger validation of variants. METHODS: We examined DNA from 100 sequentially collected probands with presumed genetic NSHL without exclusions due to inheritance, previous genetic testing, or type of hearing loss. We performed TGE using post-capture multiplexing in variable pool sizes followed by Illumina sequencing. We developed a local Galaxy installation on a high performance computing cluster for bioinformatics analysis. RESULTS: To obtain maximum variant sensitivity with this platform 3.2-6.3 million total mapped sequencing reads per sample were required. Quality score analysis showed that Sanger validation was not required for 95% of variants. Our overall diagnostic rate was 42%, but this varied by clinical features from 0% for persons with asymmetric hearing loss to 56% for persons with bilateral autosomal recessive NSHL. CONCLUSIONS: These findings will direct the use of TGE and MPS strategies for genetic diagnosis for NSHL. Our diagnostic rate highlights the need for further research on genetic deafness focused on novel gene identification and an improved understanding of the role of non-exonic mutations. The unsolved families we have identified provide a valuable resource to address these areas.

5 Article AudioGene: predicting hearing loss genotypes from phenotypes to guide genetic screening. 2013

Taylor, Kyle R / Deluca, Adam P / Shearer, A Eliot / Hildebrand, Michael S / Black-Ziegelbein, E Ann / Anand, V Nikhil / Sloan, Christina M / Eppsteiner, Robert W / Scheetz, Todd E / Huygen, Patrick L M / Smith, Richard J H / Braun, Terry A / Casavant, Thomas L. ·Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA. ·Hum Mutat · Pubmed #23280582.

ABSTRACT: Autosomal dominant nonsyndromic hearing loss (ADNSHL) is a common and often progressive sensory deficit. ADNSHL displays a high degree of genetic heterogeneity and varying rates of progression. Accurate, comprehensive, and cost-effective genetic testing facilitates genetic counseling and provides valuable prognostic information to affected individuals. In this article, we describe the algorithm underlying AudioGene, a software system employing machine-learning techniques that utilizes phenotypic information derived from audiograms to predict the genetic cause of hearing loss in persons segregating ADNSHL. Our data show that AudioGene has an accuracy of 68% in predicting the causative gene within its top three predictions, as compared with 44% for a majority classifier. We also show that AudioGene remains effective for audiograms with high levels of clinical measurement noise. We identify audiometric outliers for each genetic locus and hypothesize that outliers may reflect modifying genetic effects. As personalized genomic medicine becomes more common, AudioGene will be increasingly useful as a phenotypic filter to assess pathogenicity of variants identified by massively parallel sequencing.

6 Article Prediction of cochlear implant performance by genetic mutation: the spiral ganglion hypothesis. 2012

Eppsteiner, Robert W / Shearer, A Eliot / Hildebrand, Michael S / Deluca, Adam P / Ji, Haihong / Dunn, Camille C / Black-Ziegelbein, Elizabeth A / Casavant, Thomas L / Braun, Terry A / Scheetz, Todd E / Scherer, Steven E / Hansen, Marlan R / Gantz, Bruce J / Smith, Richard J H. ·Department of Otolaryngology - Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. ·Hear Res · Pubmed #22975204.

ABSTRACT: BACKGROUND: Up to 7% of patients with severe-to-profound deafness do not benefit from cochlear implantation. Given the high surgical implantation and clinical management cost of cochlear implantation (>$1 million lifetime cost), prospective identification of the worst performers would reduce unnecessary procedures and healthcare costs. Because cochlear implants bypass the membranous labyrinth but rely on the spiral ganglion for functionality, we hypothesize that cochlear implant (CI) performance is dictated in part by the anatomic location of the cochlear pathology that underlies the hearing loss. As a corollary, we hypothesize that because genetic testing can identify sites of cochlear pathology, it may be useful in predicting CI performance. METHODS: 29 adult CI recipients with idiopathic adult-onset severe-to-profound hearing loss were studied. DNA samples were subjected to solution-based sequence capture and massively parallel sequencing using the OtoSCOPE(®) platform. The cohort was divided into three CI performance groups (good, intermediate, poor) and genetic causes of deafness were correlated with audiometric data to determine whether there was a gene-specific impact on CI performance. RESULTS: The genetic cause of deafness was determined in 3/29 (10%) individuals. The two poor performers segregated mutations in TMPRSS3, a gene expressed in the spiral ganglion, while the good performer segregated mutations in LOXHD1, a gene expressed in the membranous labyrinth. Comprehensive literature review identified other good performers with mutations in membranous labyrinth-expressed genes; poor performance was associated with spiral ganglion-expressed genes. CONCLUSIONS: Our data support the underlying hypothesis that mutations in genes preferentially expressed in the spiral ganglion portend poor CI performance while mutations in genes expressed in the membranous labyrinth portend good CI performance. Although the low mutation rate in known deafness genes in this cohort likely relates to the ascertainment characteristics (postlingual hearing loss in adult CI recipients), these data suggest that genetic testing should be implemented as part of the CI evaluation to test this association prospectively.

7 Article Using the phenome and genome to improve genetic diagnosis for deafness. 2012

Eppsteiner, Robert W / Shearer, A Eliot / Hildebrand, Michael S / Taylor, Kyle R / Deluca, Adam P / Scherer, Steve / Huygen, Patrick / Scheetz, Todd E / Braun, Terry A / Casavant, Thomas L / Smith, Richard J H. ·Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. ·Otolaryngol Head Neck Surg · Pubmed #22785243.

ABSTRACT: -- No abstract --

8 Article Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4). 2011

Zheng, Jing / Miller, Katharine K / Yang, Tao / Hildebrand, Michael S / Shearer, A Eliot / DeLuca, Adam P / Scheetz, Todd E / Drummond, Jennifer / Scherer, Steve E / Legan, P Kevin / Goodyear, Richard J / Richardson, Guy P / Cheatham, Mary Ann / Smith, Richard J / Dallos, Peter. ·Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. ·Proc Natl Acad Sci U S A · Pubmed #21368133.

ABSTRACT: We report on a secreted protein found in mammalian cochlear outer hair cells (OHC) that is a member of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of adhesion proteins. Ceacam16 mRNA is expressed in OHC, and its protein product localizes to the tips of the tallest stereocilia and the tectorial membrane (TM). This specific localization suggests a role in maintaining the integrity of the TM as well as in the connection between the OHC stereocilia and TM, a linkage essential for mechanical amplification. In agreement with this role, CEACAM16 colocalizes and coimmunoprecipitates with the TM protein α-tectorin. In addition, we show that mutation of CEACAM16 leads to autosomal dominant nonsyndromic deafness (ADNSHL) at the autosomal dominant hearing loss (DFNA4) locus. In aggregate, these data identify CEACAM16 as an α-tectorin-interacting protein that concentrates at the point of attachment of the TM to the stereocilia and, when mutated, results in ADNSHL at the DFNA4 locus.

9 Article Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing. 2010

Shearer, A Eliot / DeLuca, Adam P / Hildebrand, Michael S / Taylor, Kyle R / Gurrola, José / Scherer, Steve / Scheetz, Todd E / Smith, Richard J H. ·Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA. ·Proc Natl Acad Sci U S A · Pubmed #21078986.

ABSTRACT: The extreme genetic heterogeneity of nonsyndromic hearing loss (NSHL) makes genetic diagnosis expensive and time consuming using available methods. To assess the feasibility of target-enrichment and massively parallel sequencing technologies to interrogate all exons of all genes implicated in NSHL, we tested nine patients diagnosed with hearing loss. Solid-phase (NimbleGen) or solution-based (SureSelect) sequence capture, followed by 454 or Illumina sequencing, respectively, were compared. Sequencing reads were mapped using GSMAPPER, BFAST, and BOWTIE, and pathogenic variants were identified using a custom-variant calling and annotation pipeline (ASAP) that incorporates publicly available in silico pathogenicity prediction tools (SIFT, BLOSUM, Polyphen2, and Align-GVGD). Samples included one negative control, three positive controls (one biological replicate), and six unknowns (10 samples total), in which we genotyped 605 single nucleotide polymorphisms (SNPs) by Sanger sequencing to measure sensitivity and specificity for SureSelect-Illumina and NimbleGen-454 methods at saturating sequence coverage. Causative mutations were identified in the positive controls but not in the negative control. In five of six idiopathic hearing loss patients we identified the pathogenic mutation. Massively parallel sequencing technologies provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss.