Genetic Deafness in the Alumni of Gallaudet University

Summary

Principal Investigator: Kathleen Arnos
Abstract: [unreadable] DESCRIPTION (provided by investigator): Hearing loss has many known genetic and environmental causes and affects at least 30 percent of the population at some time in their lives. The incidence of profound deafness at birth is about 0.8 per 1000. However, newborn hearing screening programs have shown that another 1-2 infants per 1000 have a lesser but clinically significant loss of 30dB or more in at least one ear. A remarkable feature of the genetic epidemiology of deafness was the recent discovery that, although there are many genes that can cause deafness, in many countries recessive mutations at a single locus, DFNB1, involving the GJB2 gene, which encodes the gap junction protein connexin 26, account for 30-40 percent of all cases. In 1898, E.A. Fay, a professor at Gallaudet University, published his monumental treatise "Marriages Among the Deaf in America" in which he documented hearing loss in the families of nearly 5000 marriages of the deaf in America during the 19th century. This powerful data set has been repeatedly re-analyzed during the past 100 years, and remains unique because the families were ascertained by complete selection through deaf parents. Our goal is to extend Fay's study by combining family histories obtained from Gallaudet alumni with more contemporary clinical and molecular phenotyping for GJB2 and other genes. We propose to systematically ascertain Gallaudet alumni and obtain questionnaire data as well as blood samples, which will allow us to characterize the frequency, clinical phenotype and spectrum of mutations at specific gene loci for syndromic and non- syndromic deafness. The resulting data will provide key observations on the secular trends in demographic and epidemiologic variables. We also will obtain contemporary estimates of the frequency of non-complementary (producing only deaf children) matings between deaf partners. The genotypic characterization of marriages among the deaf represents a novel strategy to search for interactions between rare non-allelic genes. This is a research opportunity, which is rapidly diminishing, as educational mainstreaming and the use of cochlear implants continue to erode the deaf culture, making matings between deaf partners less likely in the future. [unreadable] [unreadable]
Funding Period: 2004-04-15 - 2010-02-28
more information: NIH RePORT

Top Publications

  1. ncbi Newborn hearing screening--a silent revolution
    Cynthia C Morton
    Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women s Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 354:2151-64. 2006
  2. ncbi Etiology of unilateral hearing loss in a national hereditary deafness repository
    Kelley M Dodson
    Department of Otolaryngology, Virginia Commonwealth University, Richmond, VA 23298, USA
    Am J Otolaryngol 33:590-4. 2012
  3. pmc Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment
    Nanna D Rendtorff
    Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Denmark
    Am J Med Genet A 155:1298-313. 2011
  4. pmc Vestibular dysfunction in DFNB1 deafness
    Kelley M Dodson
    Department of Otolaryngology, Virginia Commonwealth University, Richmond, USA
    Am J Med Genet A 155:993-1000. 2011
  5. pmc Fitness among individuals with early childhood deafness: Studies in alumni families from Gallaudet University
    Susan H Blanton
    Hussman Institute for Human Genomics, University of Miami, FL 33136, USA
    Ann Hum Genet 74:27-33. 2010
  6. pmc A comparative analysis of the genetic epidemiology of deafness in the United States in two sets of pedigrees collected more than a century apart
    Kathleen S Arnos
    Department of Biology, Gallaudet University, Washington, DC 20002, USA
    Am J Hum Genet 83:200-7. 2008
  7. ncbi Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature
    Katherine O Welch
    Department of Biology, Gallaudet University, Washington, District of Columbia 20002, USA
    Am J Med Genet A 143:1567-73. 2007
  8. ncbi A focus group study of consumer attitudes toward genetic testing and newborn screening for deafness
    Sarah K Burton
    Genetics Program, Department of Biology, Gallaudet University, Washington, DC, USA
    Genet Med 8:779-83. 2006
  9. ncbi Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness
    Virginia W Norris
    Department of Biology, Gallaudet University, Washington, DC 20002, USA
    Ear Hear 27:732-41. 2006
  10. ncbi Education in the genetics of hearing loss: a survey of early hearing detection and intervention programs
    Sarah K Burton
    Genetics Program, Department of Biology, Gallaudet University, Washington, DC, USA
    Genet Med 8:510-7. 2006

Detail Information

Publications11

  1. ncbi Newborn hearing screening--a silent revolution
    Cynthia C Morton
    Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women s Hospital and Harvard Medical School, Boston, USA
    N Engl J Med 354:2151-64. 2006
  2. ncbi Etiology of unilateral hearing loss in a national hereditary deafness repository
    Kelley M Dodson
    Department of Otolaryngology, Virginia Commonwealth University, Richmond, VA 23298, USA
    Am J Otolaryngol 33:590-4. 2012
    ..The aim of this study was to characterize the genetic, audiologic, and epidemiologic characteristics of unilateral hearing loss (HL) in a national hereditary deafness repository...
  3. pmc Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment
    Nanna D Rendtorff
    Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Denmark
    Am J Med Genet A 155:1298-313. 2011
    ..R445H mutation in OPA1. Our findings suggest that patients who are heterozygous for WFS1 missense mutations should be carefully clinically examined for OA and other manifestations of Wolfram syndrome...
  4. pmc Vestibular dysfunction in DFNB1 deafness
    Kelley M Dodson
    Department of Otolaryngology, Virginia Commonwealth University, Richmond, USA
    Am J Med Genet A 155:993-1000. 2011
    ..We conclude that vestibular dysfunction appears to be more common in DFNB1 deafness than previously recognized and affects activities of daily living in many patients...
  5. pmc Fitness among individuals with early childhood deafness: Studies in alumni families from Gallaudet University
    Susan H Blanton
    Hussman Institute for Human Genomics, University of Miami, FL 33136, USA
    Ann Hum Genet 74:27-33. 2010
    ..11) than matings of a deaf and hearing individual (1.85), suggesting that fertility among deaf individuals is influenced by multiple factors...
  6. pmc A comparative analysis of the genetic epidemiology of deafness in the United States in two sets of pedigrees collected more than a century apart
    Kathleen S Arnos
    Department of Biology, Gallaudet University, Washington, DC 20002, USA
    Am J Hum Genet 83:200-7. 2008
    ....
  7. ncbi Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature
    Katherine O Welch
    Department of Biology, Gallaudet University, Washington, District of Columbia 20002, USA
    Am J Med Genet A 143:1567-73. 2007
    ..The difference in phenotype may be a result of the disruption of different functions of the gap-junction protein by the two mutations, which have an additive effect...
  8. ncbi A focus group study of consumer attitudes toward genetic testing and newborn screening for deafness
    Sarah K Burton
    Genetics Program, Department of Biology, Gallaudet University, Washington, DC, USA
    Genet Med 8:779-83. 2006
    ..Efforts to assess consumer attitudes toward these advances have lagged behind...
  9. ncbi Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness
    Virginia W Norris
    Department of Biology, Gallaudet University, Washington, DC 20002, USA
    Ear Hear 27:732-41. 2006
    ..The objective of this study is to document nine additional children with two pathogenic GJB2 mutations who had non penetrance of hearing loss at birth...
  10. ncbi Education in the genetics of hearing loss: a survey of early hearing detection and intervention programs
    Sarah K Burton
    Genetics Program, Department of Biology, Gallaudet University, Washington, DC, USA
    Genet Med 8:510-7. 2006
    ....
  11. ncbi The clinical and audiologic features of hearing loss due to mitochondrial mutations
    Joshua C Yelverton
    Virginia Commonwealth University Health Systems, Department of Otolaryngology Head and Neck Surgery, 1200 East Broad St, West Hospital, Richmond, Virginia 23298 0146, USA
    Otolaryngol Head Neck Surg 148:1017-22. 2013
    ....