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Hearing Disorders: HELP
Articles by Paul T. Ranum
Based on 4 articles published since 2009
(Why 4 articles?)
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Between 2009 and 2019, Paul T. Ranum wrote the following 4 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation. 2018

Yoshimura, Hidekane / Shibata, Seiji B / Ranum, Paul T / Smith, Richard J H. ·Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. · Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan. · Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. · Interdisciplinary Graduate Program in Molecular & Cellular Biology, The University of Iowa Graduate College, University of Iowa, Iowa City, IA, 52242, USA. · Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu. · Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu. · Interdisciplinary Graduate Program in Molecular & Cellular Biology, The University of Iowa Graduate College, University of Iowa, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu. · Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu. ·Sci Rep · Pubmed #29445157.

ABSTRACT: Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits robust eGFP transduction of virtually all inner hair cells throughout the cochlea with variable transduction of vestibular hair cells. Auditory thresholds are not compromised. Transduction rate and cell tropism is primarily influenced by viral titer and AAV serotype but not age at injection. This approach is safe, versatile and efficient. Its use will facilitate studies using cochlear gene therapy in murine models of hearing loss over a wide range of time points.

2 Article RNA Interference Prevents Autosomal-Dominant Hearing Loss. 2016

Shibata, Seiji B / Ranum, Paul T / Moteki, Hideaki / Pan, Bifeng / Goodwin, Alexander T / Goodman, Shawn S / Abbas, Paul J / Holt, Jeffrey R / Smith, Richard J H. ·Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. · Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Molecular & Cellular Biology, Graduate College, University of Iowa, Iowa City, IA 52242, USA. · Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Nagano 3908621, Japan. · Department of Otolaryngology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. · Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. · Department of Communication Sciences and Disorders, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA 52242, USA. · Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Molecular Otolaryngology and Renal Research Laboratories, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Interdisciplinary Graduate Program in Molecular & Cellular Biology, Graduate College, University of Iowa, Iowa City, IA 52242, USA; Iowa Institute of Human Genetics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address: richard-smith@uiowa.edu. ·Am J Hum Genet · Pubmed #27236922.

ABSTRACT: Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.

3 Article Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. 2016

Sloan-Heggen, Christina M / Bierer, Amanda O / Shearer, A Eliot / Kolbe, Diana L / Nishimura, Carla J / Frees, Kathy L / Ephraim, Sean S / Shibata, Seiji B / Booth, Kevin T / Campbell, Colleen A / Ranum, Paul T / Weaver, Amy E / Black-Ziegelbein, E Ann / Wang, Donghong / Azaiez, Hela / Smith, Richard J H. ·Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USA. · Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, 52242, IA, USA. · Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA, 52242, USA. richard-smith@uiowa.edu. · Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, 52242, IA, USA. richard-smith@uiowa.edu. · Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, 52242, IA, USA. richard-smith@uiowa.edu. ·Hum Genet · Pubmed #26969326.

ABSTRACT: Hearing loss is the most common sensory deficit in humans, affecting 1 in 500 newborns. Due to its genetic heterogeneity, comprehensive diagnostic testing has not previously been completed in a large multiethnic cohort. To determine the aggregate contribution inheritance makes to non-syndromic hearing loss, we performed comprehensive clinical genetic testing with targeted genomic enrichment and massively parallel sequencing on 1119 sequentially accrued patients. No patient was excluded based on phenotype, inheritance or previous testing. Testing resulted in identification of the underlying genetic cause for hearing loss in 440 patients (39%). Pathogenic variants were found in 49 genes and included missense variants (49%), large copy number changes (18%), small insertions and deletions (18%), nonsense variants (8%), splice-site alterations (6%), and promoter variants (<1%). The diagnostic rate varied considerably based on phenotype and was highest for patients with a positive family history of hearing loss or when the loss was congenital and symmetric. The spectrum of implicated genes showed wide ethnic variability. These findings support the more efficient utilization of medical resources through the development of evidence-based algorithms for the diagnosis of hearing loss.

4 Article HOMER2, a stereociliary scaffolding protein, is essential for normal hearing in humans and mice. 2015

Azaiez, Hela / Decker, Amanda R / Booth, Kevin T / Simpson, Allen C / Shearer, A Eliot / Huygen, Patrick L M / Bu, Fengxiao / Hildebrand, Michael S / Ranum, Paul T / Shibata, Seiji B / Turner, Ann / Zhang, Yuzhou / Kimberling, William J / Cornell, Robert A / Smith, Richard J H. ·Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology University of Iowa, Iowa City, Iowa, United States of America. · Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America. · Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. · Austin Health, Department of Medicine, University of Melbourne, Melbourne, Australia. · Self-employed physician, Menlo Park, California, United States of America. · Molecular Otolaryngology and Renal Research Laboratories, Department of Otolaryngology University of Iowa, Iowa City, Iowa, United States of America; Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, Iowa, United States of America. ·PLoS Genet · Pubmed #25816005.

ABSTRACT: Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS) the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL). After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action.