Connexin-26 mutations in sporadic and inherited sensorineural deafness

Xavier P. Estivill, Paolo Fortina, Saul Surrey, Raquel Rabionet, Salvatore Melchionda, Leonardo D'Agruma, Elaine Mansfield, Eric Rappaport, Nancy Govea, Montse Milà, Leopoldo Zelante, Paolo Gasparini

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Abstract

Background. Hearing impairment affects one infant in 1000 and 4% of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80% of Mediterranean families and that the connexin-26 gene gap junction protein β2 (GJB2) is mutated in DFNB1 families. We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness. Methods. We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG. Findings. 49% of participants with recessive deafness and 37% of sporadic cases had mutations in the GJB2 gene. The 35delG mutation accounted for 85% of GJB2 mutations, six other mutations accounted for 6% of alleles, and no changes in the coding region of GJB2 were detected in 9% of DFNB1 alleles. The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87). Interpretation. Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.

Original languageEnglish
Pages (from-to)394-398
Number of pages5
JournalLancet
Volume351
Issue number9100
DOIs
Publication statusPublished - 7 Feb 1998
Externally publishedYes

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Deafness
Mutation
Genes
Spain
Italy
Alleles
Connexin 26
Chromosomes, Human, Pair 13
Frameshift Mutation
Connexins
Mutation Rate
Hearing Loss
Population
Counseling
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Estivill, X. P., Fortina, P., Surrey, S., Rabionet, R., Melchionda, S., D'Agruma, L., ... Gasparini, P. (1998). Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet, 351(9100), 394-398. https://doi.org/10.1016/S0140-6736(97)11124-2

Connexin-26 mutations in sporadic and inherited sensorineural deafness. / Estivill, Xavier P.; Fortina, Paolo; Surrey, Saul; Rabionet, Raquel; Melchionda, Salvatore; D'Agruma, Leonardo; Mansfield, Elaine; Rappaport, Eric; Govea, Nancy; Milà, Montse; Zelante, Leopoldo; Gasparini, Paolo.

In: Lancet, Vol. 351, No. 9100, 07.02.1998, p. 394-398.

Research output: Contribution to journalArticle

Estivill, XP, Fortina, P, Surrey, S, Rabionet, R, Melchionda, S, D'Agruma, L, Mansfield, E, Rappaport, E, Govea, N, Milà, M, Zelante, L & Gasparini, P 1998, 'Connexin-26 mutations in sporadic and inherited sensorineural deafness', Lancet, vol. 351, no. 9100, pp. 394-398. https://doi.org/10.1016/S0140-6736(97)11124-2
Estivill XP, Fortina P, Surrey S, Rabionet R, Melchionda S, D'Agruma L et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet. 1998 Feb 7;351(9100):394-398. https://doi.org/10.1016/S0140-6736(97)11124-2
Estivill, Xavier P. ; Fortina, Paolo ; Surrey, Saul ; Rabionet, Raquel ; Melchionda, Salvatore ; D'Agruma, Leonardo ; Mansfield, Elaine ; Rappaport, Eric ; Govea, Nancy ; Milà, Montse ; Zelante, Leopoldo ; Gasparini, Paolo. / Connexin-26 mutations in sporadic and inherited sensorineural deafness. In: Lancet. 1998 ; Vol. 351, No. 9100. pp. 394-398.
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abstract = "Background. Hearing impairment affects one infant in 1000 and 4{\%} of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80{\%} of Mediterranean families and that the connexin-26 gene gap junction protein β2 (GJB2) is mutated in DFNB1 families. We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness. Methods. We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG. Findings. 49{\%} of participants with recessive deafness and 37{\%} of sporadic cases had mutations in the GJB2 gene. The 35delG mutation accounted for 85{\%} of GJB2 mutations, six other mutations accounted for 6{\%} of alleles, and no changes in the coding region of GJB2 were detected in 9{\%} of DFNB1 alleles. The carrier frequency of mutation 35delG among people from the general population was one in 31 (95{\%} CI one in 19 to one in 87). Interpretation. Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.",
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T1 - Connexin-26 mutations in sporadic and inherited sensorineural deafness

AU - Estivill, Xavier P.

AU - Fortina, Paolo

AU - Surrey, Saul

AU - Rabionet, Raquel

AU - Melchionda, Salvatore

AU - D'Agruma, Leonardo

AU - Mansfield, Elaine

AU - Rappaport, Eric

AU - Govea, Nancy

AU - Milà, Montse

AU - Zelante, Leopoldo

AU - Gasparini, Paolo

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Y1 - 1998/2/7

N2 - Background. Hearing impairment affects one infant in 1000 and 4% of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80% of Mediterranean families and that the connexin-26 gene gap junction protein β2 (GJB2) is mutated in DFNB1 families. We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness. Methods. We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG. Findings. 49% of participants with recessive deafness and 37% of sporadic cases had mutations in the GJB2 gene. The 35delG mutation accounted for 85% of GJB2 mutations, six other mutations accounted for 6% of alleles, and no changes in the coding region of GJB2 were detected in 9% of DFNB1 alleles. The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87). Interpretation. Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.

AB - Background. Hearing impairment affects one infant in 1000 and 4% of people aged younger than 45 years. Congenital deafness is inherited or apparently sporadic. We have shown previously that DFNB1 on chromosome 13 is a major locus for recessive deafness in about 80% of Mediterranean families and that the connexin-26 gene gap junction protein β2 (GJB2) is mutated in DFNB1 families. We investigated mutations in the GJB2 gene in familial and sporadic cases of deafness. Methods. We obtained DNA samples from 82 families from Italy and Spain with recessive non-syndromic deafness and from 54 unrelated participants with apparently sporadic congenital deafness. We analysed the coding region of the GJB2 gene for mutations. We also tested 280 unrelated people from the general populations of Italy and Spain for the frameshift mutation 35delG. Findings. 49% of participants with recessive deafness and 37% of sporadic cases had mutations in the GJB2 gene. The 35delG mutation accounted for 85% of GJB2 mutations, six other mutations accounted for 6% of alleles, and no changes in the coding region of GJB2 were detected in 9% of DFNB1 alleles. The carrier frequency of mutation 35delG among people from the general population was one in 31 (95% CI one in 19 to one in 87). Interpretation. Mutations in the GJB2 gene are a major cause of inherited and apparently sporadic congenital deafness. Mutation 35delG is the most common mutation for sensorineural deafness. identification of 35delG and other mutations in the GJB2 gene should facilitate diagnosis and counselling for the most common genetic form of deafness.

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JF - The Lancet

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