Non-Syndromic Hearing Loss -- A Collaborative Study

Summary

Principal Investigator: Richard J Smith
Affiliation: University of Iowa
Country: USA
Abstract: DESCRIPTION (provided by applicant): Advances in the molecular genetics of deafness have vastly improved our ability to identify heritable hearing losses. Most familial moderate-to-profound congenital losses are inherited as an autosomal recessive trait. Heterogeneity is high, and to date 77 non-syndromic recessive loci have been identified and numbered sequentially DFNB1 through DFNB77 (DFN, deafness;B, recessive;integer, order of discovery). Twenty-eight causally-related genes have been cloned and encode proteins with a wide range of functions. Mutations in one gene, GJB2 at the DFNB1 locus, are responsible for half of moderate-to-profound autosomal recessive non-syndromic deafness (ARNSD) in many developed countries, making DFNB1 the most common type of hereditary congenital hearing loss. Mutations in SLC26A4 at the DFNB4 locus rank second and are associated with a Pendred Syndrome (PS)-DFNB4 phenotype. In aggregate, these advances have numerous important consequences. First, the identification of genes essential for normal auditory function has provided valuable insight into inner ear physiology at the molecular level and may one day lead to the development of novel therapies to treat deafness. Second, the use of genetic testing to diagnose ARNSD has changed the medical evaluation of the deaf person. Third, the identification of numerous genes that cause ARNSD, coupled with recent technological advances in microarray sequence capture and deep sequencing, is now making epidemiological studies of genetic deafness possible for the first time. This renewal application will focus on these three areas by completing specific aims: (1) To identify novel ARNSD genes;(2) To complete mutation screening of all genes implicated in non-syndromic deafness;(3) To study PS-DFNB4 as a complex disease. Completion of these specific aims will not only increase our understanding of the biology of hearing and deafness, but will be highly translational by improving the clinical diagnosis of non-syndromic deafness. PUBLIC HEALTH RELEVANCE: Autosomal recessive non-syndromic deafness (ARNSD) is extremely heterogeneous. To date 77 loci have been identified and 28 causally-related genes have been cloned. Studying these genes will increase our understanding of deafness, improve patient care, and ultimately lead to novel methods of treating ARNSD.
Funding Period: ----------------1996 - ---------------2014-
more information: NIH RePORT

Top Publications

  1. pmc OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele
    R Varga
    Center for Hereditary Communication Disorders, Boys Town National Research Hospital BTNRH, Omaha, NE, USA
    J Med Genet 43:576-81. 2006
  2. doi Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11
    N Hilgert
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Clin Genet 74:223-32. 2008
  3. pmc AudioGene: predicting hearing loss genotypes from phenotypes to guide genetic screening
    Kyle R Taylor
    Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA
    Hum Mutat 34:539-45. 2013
  4. pmc Pre-capture multiplexing improves efficiency and cost-effectiveness of targeted genomic enrichment
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
    BMC Genomics 13:618. 2012
  5. pmc Genetics: advances in genetic testing for deafness
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
    Curr Opin Pediatr 24:679-86. 2012
  6. pmc High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects
    Mariem Ben Saïd
    Targets for Diagnosis and Therapy Unit, Centre of Biotechnology of Sfax, Sfax, Tunisia
    Genet Test Mol Biomarkers 14:307-11. 2010
  7. pmc Solution-based targeted genomic enrichment for precious DNA samples
    Aiden Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
    BMC Biotechnol 12:20. 2012
  8. ncbi Genetic disorders of the vestibular system
    Robert W Eppsteiner
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
    Curr Opin Otolaryngol Head Neck Surg 19:397-402. 2011
  9. pmc Advancing genetic testing for deafness with genomic technology
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, Molecular Otolaryngology and Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
    J Med Genet 50:627-34. 2013
  10. pmc Promoter, alternative splice forms, and genomic structure of protocadherin 15
    Kumar N Alagramam
    Department of Otolaryngology Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA
    Genomics 90:482-92. 2007

Scientific Experts

  • Konrad Noben-Trauth
  • Yukihide Maeda
  • Guntram Borck
  • Richard J H Smith
  • Michael S Hildebrand
  • A Eliot Shearer
  • Hossein Najmabadi
  • Kimia Kahrizi
  • William J Kimberling
  • Nele Hilgert
  • Guy Van Camp
  • R J H Smith
  • Tao Yang
  • Nicole C Meyer
  • Yuzhou Zhang
  • Kyle R Taylor
  • Robert W Eppsteiner
  • Adam P DeLuca
  • Todd E Scheetz
  • Niloofar Bazazzadegan
  • Matthew R Avenarius
  • N Hilgert
  • Christina M Sloan
  • Dietrich Stephan
  • Jennifer A Webster
  • Melanie Bahlo
  • G Van Camp
  • Nicolas Grillet
  • Hela Azaiez
  • Martin Schwander
  • Carla J Nishimura
  • E Ann Black-Ziegelbein
  • Thomas L Casavant
  • Terry A Braun
  • Emily M LeProust
  • Swati Joshi
  • Scott Happe
  • Barbara Novak
  • Angelica C Guiffre
  • Harini Ravi
  • Aiden Eliot Shearer
  • Patrick L M Huygen
  • Nikoletta Charizopoulou
  • Jing Zheng
  • Mariem Ben Saïd
  • Carla Nishimura
  • Hana Odeh
  • E Wilch
  • M S Hildebrand
  • H Najmabadi
  • Mustafa Tekin
  • K Kahrizi
  • Ahmad Daneshi
  • Arabandi Ramesh
  • Yoko Nakano
  • Philine Wangemann
  • Richard J Smith
  • Thomas B Friedman
  • N Dieltjens
  • Saima Riazuddin
  • Tim Wiltshire
  • W J Kimberling
  • Anna Sczaniecka
  • Lisa M Tarantino
  • Marzieh Mohseni
  • Ulrich Muller
  • Payman Jamali
  • Kumar N Alagramam
  • Mahdi Malekpour
  • Shahid Y Khan
  • Amit Kochhar
  • N C Meyer
  • Rick F Nelson
  • Katherine J D A Excoffon
  • R Varga
  • V Nikhil Anand
  • Susanna D Howard
  • Margit Schraders
  • Kausik Ray
  • Ronald J C Admiraal
  • Jeffrey R Holt
  • Harold R Neely
  • Abraham M Sheffield
  • P Kevin Legan
  • Guy P Richardson
  • Andrea Lelli
  • C R Srikumari Srisailapathy
  • Peter Dallos
  • Richard J Goodyear
  • Joseph R Latoche

Detail Information

Publications45

  1. pmc OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele
    R Varga
    Center for Hereditary Communication Disorders, Boys Town National Research Hospital BTNRH, Omaha, NE, USA
    J Med Genet 43:576-81. 2006
    ..Among the second tier genetic causes of hearing loss in children are mutations in the DFNB9/OTOF gene...
  2. doi Mutation analysis of TMC1 identifies four new mutations and suggests an additional deafness gene at loci DFNA36 and DFNB7/11
    N Hilgert
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Clin Genet 74:223-32. 2008
    ..The analysis of copy number variations in TMC1 as well as DNA sequencing of 15 additional candidate genes did not reveal any proven pathogenic changes, leaving both hypotheses open...
  3. pmc AudioGene: predicting hearing loss genotypes from phenotypes to guide genetic screening
    Kyle R Taylor
    Department of Electrical and Computer Engineering, University of Iowa, Iowa City, IA, USA
    Hum Mutat 34:539-45. 2013
    ..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...
  4. pmc Pre-capture multiplexing improves efficiency and cost-effectiveness of targeted genomic enrichment
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
    BMC Genomics 13:618. 2012
    ..Our overall goal was to maximize cost reduction and minimize experimental time while maintaining a high percentage of reads on target and a high depth of coverage at thresholds required for variant detection...
  5. pmc Genetics: advances in genetic testing for deafness
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
    Curr Opin Pediatr 24:679-86. 2012
    ..To provide an update on recently discovered human deafness genes and to describe advances in comprehensive genetic testing platforms for deafness, both of which have been enabled by new massively parallel sequencing technologies...
  6. pmc High frequency of the p.R34X mutation in the TMC1 gene associated with nonsyndromic hearing loss is due to founder effects
    Mariem Ben Saïd
    Targets for Diagnosis and Therapy Unit, Centre of Biotechnology of Sfax, Sfax, Tunisia
    Genet Test Mol Biomarkers 14:307-11. 2010
    ..Screening for the TMC1 p.R34X mutation is indicated in the genetic evaluation of persons with ARNSHL from North African and Southwest Asia...
  7. pmc Solution-based targeted genomic enrichment for precious DNA samples
    Aiden Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
    BMC Biotechnol 12:20. 2012
    ..These protocols could be improved by: 1) modifying or eliminating time consuming steps; 2) increasing yield to reduce input DNA and excessive PCR cycling; and 3) enhancing reproducible...
  8. ncbi Genetic disorders of the vestibular system
    Robert W Eppsteiner
    Department of Otolaryngology Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
    Curr Opin Otolaryngol Head Neck Surg 19:397-402. 2011
    ..We emphasize peripheral causes of vestibular dysfunction and highlight recent advances in the field, point out gaps in understanding, and focus on key areas for future investigation...
  9. pmc Advancing genetic testing for deafness with genomic technology
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, Molecular Otolaryngology and Renal Research Labs, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
    J Med Genet 50:627-34. 2013
    ....
  10. pmc Promoter, alternative splice forms, and genomic structure of protocadherin 15
    Kumar N Alagramam
    Department of Otolaryngology Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA
    Genomics 90:482-92. 2007
    ..Results from our study show that both mouse and human protocadherin 15 genes have complex genomic structures and transcription control mechanisms...
  11. ncbi Genotype-phenotype correlations for SLC26A4-related deafness
    Hela Azaiez
    Molecular Otolaryngology Research Laboratories, Department of Otolaryngology Head and Neck Surgery, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242, USA
    Hum Genet 122:451-7. 2007
    ..For all patients, variability in the degree of hearing loss is seen across genotypes implicating other genetic and/or environmental factors in the pathogenesis of the PS-Mondini-EVA disease spectrum...
  12. ncbi Clinical aspects of hereditary hearing loss
    Amit Kochhar
    Molecular Otolaryngology Research Laboratories, University of Iowa, Iowa City, Iowa 52242, USA
    Genet Med 9:393-408. 2007
    ..The aim of this review is to provide a comprehensive framework underlying the causes of hearing impairment and to detail the clinical management for patients with hereditary hearing loss...
  13. ncbi The Coxsackievirus and Adenovirus Receptor: a new adhesion protein in cochlear development
    Katherine J D A Excoffon
    Department of Internal Medicine, Division of Pulmonary Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA
    Hear Res 215:1-9. 2006
    ....
  14. pmc Sensorineural deafness and male infertility: a contiguous gene deletion syndrome
    Yuzhou Zhang
    Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa 52240, USA
    J Med Genet 44:233-40. 2007
    ..Syndromic hearing loss that results from contiguous gene deletions is uncommon. Deafness-infertility syndrome (DIS) is caused by large contiguous gene deletions at 15q15.3...
  15. ncbi Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus
    Shahid Y Khan
    National Centre of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan
    Hum Mutat 28:417-23. 2007
    ..Further, high-resolution confocal microscopy in mouse inner ear demonstrates that radixin is expressed along the length of stereocilia of hair cells from both the organ of Corti and the vestibular system...
  16. ncbi A forward genetics screen in mice identifies recessive deafness traits and reveals that pejvakin is essential for outer hair cell function
    Martin Schwander
    Department of Cell Biology, Institute for Childhood and Neglected Disease, The Scripps Research Institute, La Jolla, California 92037, USA
    J Neurosci 27:2163-75. 2007
    ....
  17. ncbi Identification of three novel TECTA mutations in Iranian families with autosomal recessive nonsyndromic hearing impairment at the DFNB21 locus
    Nicole C Meyer
    Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA
    Am J Med Genet A 143:1623-9. 2007
    ..The truncating nature of these mutations is consistent with loss-of-function, and therefore the existing TECTA knockout mouse mutant represents a good model in which to study DFNB21-related deafness...
  18. ncbi Selective cochlear degeneration in mice lacking the F-box protein, Fbx2, a glycoprotein-specific ubiquitin ligase subunit
    Rick F Nelson
    Medical Scientist Training Program, University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, Iowa 52242, USA
    J Neurosci 27:5163-71. 2007
    ..Our findings demonstrate that components of protein quality control are essential for inner ear homeostasis and implicate Fbx2 and Skp1 as potential genetic modifiers in age-related hearing loss...
  19. ncbi Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree
    N C Meyer
    Department of Otolaryngology, Carver College of Medicine, The University of Iowa, Iowa City, IA 52242, USA
    Clin Genet 72:130-7. 2007
    ..Val37Ile and p.Leu90Pro mutations in Connexin 26. One nuclear family in the extended pedigree segregates both dominant and recessive non-syndromic hearing loss...
  20. pmc Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing children
    William J Kimberling
    Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska 68131, USA
    Genet Med 12:512-6. 2010
    ....
  21. pmc Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4)
    Tao Yang
    Department of Otolaryngology Head and Neck, University of Iowa, Iowa City, IA 52242, USA
    Am J Hum Genet 80:1055-63. 2007
    ..These results support a novel dosage-dependent model for the molecular pathogenesis of PS and nonsyndromic EVA that involves SLC26A4 and its transcriptional regulatory machinery...
  22. pmc Loss-of-function mutations of ILDR1 cause autosomal-recessive hearing impairment DFNB42
    Guntram Borck
    Institute of Human Genetics, University of Cologne, Cologne, Germany
    Am J Hum Genet 88:127-37. 2011
    ..These data identify loss-of-function mutations of ILDR1, a gene with a conserved expression pattern pointing to a conserved function in hearing in vertebrates, as underlying nonsyndromic prelingual sensorineural hearing impairment...
  23. pmc Genetic male infertility and mutation of CATSPER ion channels
    Michael S Hildebrand
    Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
    Eur J Hum Genet 18:1178-84. 2010
    ..In addition, we discuss clinical management and therapeutic options for these patients. Finally, we describe how the CATSPER channel could be used as a target for development of a male contraceptive...
  24. pmc Microarray analysis of the effect of dexamethasone on murine cochlear explants
    Yukihide Maeda
    Department of Otolaryngology Head and Neck Surgery, Okayama University Graduate School of Medicine, Okayama, Japan
    Acta Otolaryngol 130:1329-34. 2010
    ..The present data may support the use of dexamethasone to treat acute sensorineural hearing loss. It is warrantable to test these results in the in vivo cochlea...
  25. pmc Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing
    A Eliot Shearer
    Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 107:21104-9. 2010
    ..Massively parallel sequencing technologies provide sensitivity, specificity, and reproducibility at levels sufficient to perform genetic diagnosis of hearing loss...
  26. pmc Mutations in TMC1 are a common cause of DFNB7/11 hearing loss in the Iranian population
    Michael S Hildebrand
    Department of Otolaryngology Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
    Ann Otol Rhinol Laryngol 119:830-5. 2010
    ..We investigated the cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) that segregated in 2 consanguineous Iranian families...
  27. pmc Deafness in the genomics era
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USA
    Hear Res 282:1-9. 2011
    ..We review commonly used genomic technologies as well as the application of these technologies to the genetic diagnosis of hereditary hearing loss and to the discovery of novel deafness genes...
  28. pmc Carcinoembryonic antigen-related cell adhesion molecule 16 interacts with alpha-tectorin and is mutated in autosomal dominant hearing loss (DFNA4)
    Jing Zheng
    Department of Otolaryngology Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
    Proc Natl Acad Sci U S A 108:4218-23. 2011
    ..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...
  29. pmc Two Iranian families with a novel mutation in GJB2 causing autosomal dominant nonsyndromic hearing loss
    Niloofar Bazazzadegan
    Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
    Am J Med Genet A 155:1202-11. 2011
    ..This finding implicates the D46N missense mutation in Cx26 as a common cause of deafness in this part of Iran mandating mutation screening of GJB2 for D46N in all persons with hearing loss who originate from this geographic region...
  30. pmc Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human
    Nikoletta Charizopoulou
    Section on Neurogenetics, Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Maryland 20850, USA
    Nat Commun 2:201. 2011
    ..Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells...
  31. doi Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment
    Kimia Kahrizi
    Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
    Eur J Pediatr 168:651-3. 2009
    ..These results imply that Pendred syndrome is the most prevalent form of syndromic hereditary hearing loss in Iran...
  32. pmc Phenotypic variability of patients homozygous for the GJB2 mutation 35delG cannot be explained by the influence of one major modifier gene
    Nele Hilgert
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Eur J Hum Genet 17:517-24. 2009
    ..Significantly associated SNPs may reflect a small modifying effect on the phenotype. Increasing the power of the study will be of greatest importance to confirm these results...
  33. doi A large deletion in GPR98 causes type IIC Usher syndrome in male and female members of an Iranian family
    N Hilgert
    Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    J Med Genet 46:272-6. 2009
    ..USH2C is characterised by moderate to severe hearing loss, retinitis pigmentosa and normal vestibular function. One earlier report describes mutations in GPR98 (VLGR1) in four families segregating this phenotype...
  34. pmc Mutations of KCNJ10 together with mutations of SLC26A4 cause digenic nonsyndromic hearing loss associated with enlarged vestibular aqueduct syndrome
    Tao Yang
    Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, PR China
    Am J Hum Genet 84:651-7. 2009
    ..Our results link KCNJ10 mutations with EVA/PS and provide further support for the model of EVA/PS as a multigenic complex disease...
  35. pmc Function and expression pattern of nonsyndromic deafness genes
    Nele Hilgert
    Department of Medical Genetics, University of Antwerp UA, Belgium
    Curr Mol Med 9:546-64. 2009
    ..This review should provide auditory scientists the most relevant information for all identified nonsyndromic deafness genes...
  36. pmc A claudin-9-based ion permeability barrier is essential for hearing
    Yoko Nakano
    Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USA
    PLoS Genet 5:e1000610. 2009
    ..Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical) tight-junction strands have biologically important ion barrier function...
  37. pmc Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans
    Nicolas Grillet
    Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Am J Hum Genet 85:328-37. 2009
    ..LOXHD1, MYO3a, and PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL...
  38. pmc Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation
    M S Hildebrand
    Department of Otolaryngology, University of Iowa, Iowa City, IA, USA
    Clin Genet 77:563-71. 2010
    ..Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders...
  39. pmc Mutations in Grxcr1 are the basis for inner ear dysfunction in the pirouette mouse
    Hana Odeh
    Department of Otolaryngology, Kresge Hearing Research Institute, University of Michigan Medical School, Ann Arbor, MI 48109, USA
    Am J Hum Genet 86:148-60. 2010
    ..Our results suggest that deafness in pirouette mutants is associated with loss of GRXCR1 function in modulating actin cytoskeletal architecture in the developing stereocilia of sensory hair cells...
  40. pmc miRNA mutations are not a common cause of deafness
    Michael S Hildebrand
    Department of Otolaryngology Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA
    Am J Med Genet A 152:646-52. 2010
    ..These results suggest that mutations disrupting gene regulation by the miR-183 cluster are not a common cause of human hearing loss...
  41. pmc A novel DFNB1 deletion allele supports the existence of a distant cis-regulatory region that controls GJB2 and GJB6 expression
    E Wilch
    Genetics Program, Michigan State University, East Lansing, MI 48824, USA
    Clin Genet 78:267-74. 2010
    ..Characterization of distant GJB2/GJB6 cis-regulatory regions evidenced by this allele may be required to find the 'missing' DFNB1 mutations that are believed to exist...
  42. pmc Mutations in the first MyTH4 domain of MYO15A are a common cause of DFNB3 hearing loss
    A Eliot Shearer
    Department of Otolaryngology Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA
    Laryngoscope 119:727-33. 2009
    ..To use clinical and genetic analyses to determine the mutation causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in two consanguineous Iranian families...
  43. pmc Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics?
    Nele Hilgert
    Department of Medical Genetics, University of Antwerp UA, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Mutat Res 681:189-96. 2009
    ..This ability will greatly improve DNA diagnostics, provide epidemiological data on gene-based mutation frequencies, and reveal novel genotype-phenotype correlations...