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. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006707-02
Application #
6885371
Study Section
Epidemiology of Clinical Disorders and Aging Study Section (ECDA)
Program Officer
Watson, Bracie
Project Start
2004-04-15
Project End
2009-02-28
Budget Start
2005-03-01
Budget End
2006-02-28
Support Year
2
Fiscal Year
2005
Total Cost
$292,045
Indirect Cost
Name
Gallaudet University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
003259439
City
Washington
State
DC
Country
United States
Zip Code
20002
Yelverton, Joshua C; Arnos, Kathleen; Xia, Xia-Juan et al. (2013) The clinical and audiologic features of hearing loss due to mitochondrial mutations. Otolaryngol Head Neck Surg 148:1017-22
Dodson, Kelley M; Georgolios, Alexandros; Barr, Noelle et al. (2012) Etiology of unilateral hearing loss in a national hereditary deafness repository. Am J Otolaryngol 33:590-4
Rendtorff, Nanna D; Lodahl, Marianne; Boulahbel, Houda et al. (2011) Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment. Am J Med Genet A 155A:1298-313
Dodson, Kelley M; Blanton, Susan H; Welch, Katherine O et al. (2011) Vestibular dysfunction in DFNB1 deafness. Am J Med Genet A 155A:993-1000
Blanton, Susan H; Nance, Walter E; Norris, Virginia W et al. (2010) Fitness among individuals with early childhood deafness: Studies in alumni families from Gallaudet University. Ann Hum Genet 74:27-33
Arnos, Kathleen S; Welch, Katherine O; Tekin, Mustafa et al. (2008) A comparative analysis of the genetic epidemiology of deafness in the United States in two sets of pedigrees collected more than a century apart. Am J Hum Genet 83:200-7
Welch, Katherine O; Marin, Ruth S; Pandya, Arti et al. (2007) Compound heterozygosity for dominant and recessive GJB2 mutations: effect on phenotype and review of the literature. Am J Med Genet A 143A:1567-73
Morton, Cynthia C; Nance, Walter E (2006) Newborn hearing screening--a silent revolution. N Engl J Med 354:2151-64
Burton, Sarah K; Blanton, Susan H; Culpepper, Brandt et al. (2006) Education in the genetics of hearing loss: a survey of early hearing detection and intervention programs. Genet Med 8:510-7
Norris, Virginia W; Arnos, Kathleen S; Hanks, Wendy D et al. (2006) Does universal newborn hearing screening identify all children with GJB2 (Connexin 26) deafness? Penetrance of GJB2 deafness. Ear Hear 27:732-41

Showing the most recent 10 out of 12 publications