Prelingual deafness: High prevalence of a 30delG mutation in the connexin 26 gene

Françoise Denoyelle, Dominique Weil, Marion A. Maw, Stephen A. Wilcox, Nicholas J. Lench, Denise R. Allen-Powell, Amelia H. Osborn, Hans Henrik M Dahl, Anna Middleton, Mark J. Houseman, Catherine Dodé, Sandrine Marlin, Amel Boulila-ElGaïed, Mohammed Grati, Hammadi Ayadi, Saïda BenArab, Pierre Bitoun, Geneviève Lina-Granade, Jacqueline Godet, Mirna MustaphaJacques Loiselet, Élie El-Zir, Anne Aubois, Alain Joannard, Jacqueline Levilliers, Éréa Noël Garabédian, Robert F. Mueller, R. J. McKinlay Gardner, Christine Petit

Research output: Contribution to journalArticle

528 Citations (Scopus)

Abstract

Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In > 80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly Tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (~70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counselling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.

Original languageEnglish (US)
Pages (from-to)2173-2177
Number of pages5
JournalHuman Molecular Genetics
Volume6
Issue number12
DOIs
StatePublished - Nov 1997
Externally publishedYes

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Deafness
Mutation
Genes
Alleles
Founder Effect
Tunisia
Genetic Counseling
Myosins
New Zealand
France
Connexin 26

ASJC Scopus subject areas

  • Genetics

Cite this

Denoyelle, F., Weil, D., Maw, M. A., Wilcox, S. A., Lench, N. J., Allen-Powell, D. R., ... Petit, C. (1997). Prelingual deafness: High prevalence of a 30delG mutation in the connexin 26 gene. Human Molecular Genetics, 6(12), 2173-2177. https://doi.org/10.1093/hmg/6.12.2173

Prelingual deafness : High prevalence of a 30delG mutation in the connexin 26 gene. / Denoyelle, Françoise; Weil, Dominique; Maw, Marion A.; Wilcox, Stephen A.; Lench, Nicholas J.; Allen-Powell, Denise R.; Osborn, Amelia H.; Dahl, Hans Henrik M; Middleton, Anna; Houseman, Mark J.; Dodé, Catherine; Marlin, Sandrine; Boulila-ElGaïed, Amel; Grati, Mohammed; Ayadi, Hammadi; BenArab, Saïda; Bitoun, Pierre; Lina-Granade, Geneviève; Godet, Jacqueline; Mustapha, Mirna; Loiselet, Jacques; El-Zir, Élie; Aubois, Anne; Joannard, Alain; Levilliers, Jacqueline; Garabédian, Éréa Noël; Mueller, Robert F.; McKinlay Gardner, R. J.; Petit, Christine.

In: Human Molecular Genetics, Vol. 6, No. 12, 11.1997, p. 2173-2177.

Research output: Contribution to journalArticle

Denoyelle, F, Weil, D, Maw, MA, Wilcox, SA, Lench, NJ, Allen-Powell, DR, Osborn, AH, Dahl, HHM, Middleton, A, Houseman, MJ, Dodé, C, Marlin, S, Boulila-ElGaïed, A, Grati, M, Ayadi, H, BenArab, S, Bitoun, P, Lina-Granade, G, Godet, J, Mustapha, M, Loiselet, J, El-Zir, É, Aubois, A, Joannard, A, Levilliers, J, Garabédian, ÉN, Mueller, RF, McKinlay Gardner, RJ & Petit, C 1997, 'Prelingual deafness: High prevalence of a 30delG mutation in the connexin 26 gene', Human Molecular Genetics, vol. 6, no. 12, pp. 2173-2177. https://doi.org/10.1093/hmg/6.12.2173
Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR et al. Prelingual deafness: High prevalence of a 30delG mutation in the connexin 26 gene. Human Molecular Genetics. 1997 Nov;6(12):2173-2177. https://doi.org/10.1093/hmg/6.12.2173
Denoyelle, Françoise ; Weil, Dominique ; Maw, Marion A. ; Wilcox, Stephen A. ; Lench, Nicholas J. ; Allen-Powell, Denise R. ; Osborn, Amelia H. ; Dahl, Hans Henrik M ; Middleton, Anna ; Houseman, Mark J. ; Dodé, Catherine ; Marlin, Sandrine ; Boulila-ElGaïed, Amel ; Grati, Mohammed ; Ayadi, Hammadi ; BenArab, Saïda ; Bitoun, Pierre ; Lina-Granade, Geneviève ; Godet, Jacqueline ; Mustapha, Mirna ; Loiselet, Jacques ; El-Zir, Élie ; Aubois, Anne ; Joannard, Alain ; Levilliers, Jacqueline ; Garabédian, Éréa Noël ; Mueller, Robert F. ; McKinlay Gardner, R. J. ; Petit, Christine. / Prelingual deafness : High prevalence of a 30delG mutation in the connexin 26 gene. In: Human Molecular Genetics. 1997 ; Vol. 6, No. 12. pp. 2173-2177.
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abstract = "Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In > 80{\%} of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly Tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (~70{\%}) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counselling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.",
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T2 - High prevalence of a 30delG mutation in the connexin 26 gene

AU - Denoyelle, Françoise

AU - Weil, Dominique

AU - Maw, Marion A.

AU - Wilcox, Stephen A.

AU - Lench, Nicholas J.

AU - Allen-Powell, Denise R.

AU - Osborn, Amelia H.

AU - Dahl, Hans Henrik M

AU - Middleton, Anna

AU - Houseman, Mark J.

AU - Dodé, Catherine

AU - Marlin, Sandrine

AU - Boulila-ElGaïed, Amel

AU - Grati, Mohammed

AU - Ayadi, Hammadi

AU - BenArab, Saïda

AU - Bitoun, Pierre

AU - Lina-Granade, Geneviève

AU - Godet, Jacqueline

AU - Mustapha, Mirna

AU - Loiselet, Jacques

AU - El-Zir, Élie

AU - Aubois, Anne

AU - Joannard, Alain

AU - Levilliers, Jacqueline

AU - Garabédian, Éréa Noël

AU - Mueller, Robert F.

AU - McKinlay Gardner, R. J.

AU - Petit, Christine

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