Frequency and distribution of GJB2 (connexin 26) and GJBG (connexin 30) mutations in a large North American repository of deaf probands

Arti Pandya, Kathleen S. Arnos, Xia J. Xia, Katherine O. Welch, Susan H Blanton, Thomas B. Friedman, Guillermina Garcia Sanchez, Xue Z Liu, Robert Morell, Walter E. Nance

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Purpose: Profound hearing loss occurs with a frequency of 1 in 1000 live births, half of which is genetic in etiology. The past decade has witnessed rapid advances in determining the pathogenesis of both syndromic and nonsyndromic deafness. The most significant clinical finding to date has been the discovery that mutations of GJB2 at the DFNB1 locus are the major cause of profound prelingual deafness in many countries. More recently, GJB2 mutations have been shown to cause deafness when present with a deletion of the GJB6 gene. We report on the prevalence of GJB2 and GJB6 mutations in a large North American Repository of DMA from deaf probands and document the profound effects of familial ethnicity and parental mating types on the frequency of these mutations in the population. Methods: Deaf probands were ascertained through the Annual Survey of Deaf and Hard of Hearing Children and Youth, conducted at the Research Institute of Gallaudet University. Educational, etiologic, and audiologic information was collected after obtaining informed consent. DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods. Results: GJB2 mutations accounted for 22.2% of deafness in the overall sample but differed significantly among Asians, African-Americans and Hispanics and for probands from deaf by deaf and deaf by hearing matings, as well as probands from simplex and multiplex sibships of hearing-parents. In our sample, the overall incidence of GJB2/GJB6 deafness was 2.57%. Conclusion: GJB2 mutations account for a large proportion of deafness in the US, with certain mutations having a high ethnic predilection. Heterozygotes at the GJB2 locus should be screened for the GJB6 deletion as a cause of deafness. Molecular testing for GJB2 and GJB6 should be offered to all patients with nonsyndromic hearing loss.

Original languageEnglish
Pages (from-to)295-303
Number of pages9
JournalGenetics in Medicine
Volume5
Issue number4
DOIs
StatePublished - Jul 1 2003

Fingerprint

Connexins
Deafness
Mutation
Hearing
Asian Americans
Gene Deletion
Live Birth
Mutation Rate
Heterozygote
Informed Consent
Hearing Loss
Hispanic Americans
African Americans
Connexin 26
Parents
Polymerase Chain Reaction
DNA
Incidence
Population

Keywords

  • Genetic hearing loss
  • GJB2 (connexin 26)
  • GJB6 (connexin 30)
  • National DNA repository
  • Prevalence

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Frequency and distribution of GJB2 (connexin 26) and GJBG (connexin 30) mutations in a large North American repository of deaf probands. / Pandya, Arti; Arnos, Kathleen S.; Xia, Xia J.; Welch, Katherine O.; Blanton, Susan H; Friedman, Thomas B.; Garcia Sanchez, Guillermina; Liu, Xue Z; Morell, Robert; Nance, Walter E.

In: Genetics in Medicine, Vol. 5, No. 4, 01.07.2003, p. 295-303.

Research output: Contribution to journalArticle

Pandya, Arti ; Arnos, Kathleen S. ; Xia, Xia J. ; Welch, Katherine O. ; Blanton, Susan H ; Friedman, Thomas B. ; Garcia Sanchez, Guillermina ; Liu, Xue Z ; Morell, Robert ; Nance, Walter E. / Frequency and distribution of GJB2 (connexin 26) and GJBG (connexin 30) mutations in a large North American repository of deaf probands. In: Genetics in Medicine. 2003 ; Vol. 5, No. 4. pp. 295-303.
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abstract = "Purpose: Profound hearing loss occurs with a frequency of 1 in 1000 live births, half of which is genetic in etiology. The past decade has witnessed rapid advances in determining the pathogenesis of both syndromic and nonsyndromic deafness. The most significant clinical finding to date has been the discovery that mutations of GJB2 at the DFNB1 locus are the major cause of profound prelingual deafness in many countries. More recently, GJB2 mutations have been shown to cause deafness when present with a deletion of the GJB6 gene. We report on the prevalence of GJB2 and GJB6 mutations in a large North American Repository of DMA from deaf probands and document the profound effects of familial ethnicity and parental mating types on the frequency of these mutations in the population. Methods: Deaf probands were ascertained through the Annual Survey of Deaf and Hard of Hearing Children and Youth, conducted at the Research Institute of Gallaudet University. Educational, etiologic, and audiologic information was collected after obtaining informed consent. DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods. Results: GJB2 mutations accounted for 22.2{\%} of deafness in the overall sample but differed significantly among Asians, African-Americans and Hispanics and for probands from deaf by deaf and deaf by hearing matings, as well as probands from simplex and multiplex sibships of hearing-parents. In our sample, the overall incidence of GJB2/GJB6 deafness was 2.57{\%}. Conclusion: GJB2 mutations account for a large proportion of deafness in the US, with certain mutations having a high ethnic predilection. Heterozygotes at the GJB2 locus should be screened for the GJB6 deletion as a cause of deafness. Molecular testing for GJB2 and GJB6 should be offered to all patients with nonsyndromic hearing loss.",
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AU - Xia, Xia J.

AU - Welch, Katherine O.

AU - Blanton, Susan H

AU - Friedman, Thomas B.

AU - Garcia Sanchez, Guillermina

AU - Liu, Xue Z

AU - Morell, Robert

AU - Nance, Walter E.

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N2 - Purpose: Profound hearing loss occurs with a frequency of 1 in 1000 live births, half of which is genetic in etiology. The past decade has witnessed rapid advances in determining the pathogenesis of both syndromic and nonsyndromic deafness. The most significant clinical finding to date has been the discovery that mutations of GJB2 at the DFNB1 locus are the major cause of profound prelingual deafness in many countries. More recently, GJB2 mutations have been shown to cause deafness when present with a deletion of the GJB6 gene. We report on the prevalence of GJB2 and GJB6 mutations in a large North American Repository of DMA from deaf probands and document the profound effects of familial ethnicity and parental mating types on the frequency of these mutations in the population. Methods: Deaf probands were ascertained through the Annual Survey of Deaf and Hard of Hearing Children and Youth, conducted at the Research Institute of Gallaudet University. Educational, etiologic, and audiologic information was collected after obtaining informed consent. DNA studies were performed for the GJB2 and GJB6 loci by sequencing and PCR methods. Results: GJB2 mutations accounted for 22.2% of deafness in the overall sample but differed significantly among Asians, African-Americans and Hispanics and for probands from deaf by deaf and deaf by hearing matings, as well as probands from simplex and multiplex sibships of hearing-parents. In our sample, the overall incidence of GJB2/GJB6 deafness was 2.57%. Conclusion: GJB2 mutations account for a large proportion of deafness in the US, with certain mutations having a high ethnic predilection. Heterozygotes at the GJB2 locus should be screened for the GJB6 deletion as a cause of deafness. Molecular testing for GJB2 and GJB6 should be offered to all patients with nonsyndromic hearing loss.

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