Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness

Robert J. Morell, Hung Jeff Kim, Linda J. Hood, Leah Goforth, Karen Friderici, Rachel Fisher, Guy Van Camp, Charles I. Berlin, Carole Oddoux, Harry Ostrer, Bronya Keats, Thomas B. Friedman, Theresa San Agustin, Jan Dumon

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Abstract

Background. Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods. We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle- ear immittance, and recording of otoacoustic emissions. Results. Two frame- shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. Conclusions. The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations.

Original languageEnglish (US)
Pages (from-to)1500-1505
Number of pages6
JournalNew England Journal of Medicine
Volume339
Issue number21
DOIs
StatePublished - Nov 19 1998
Externally publishedYes

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Jews
Mutation
Haplotypes
Genes
Alleles
Hearing
Persons With Hearing Impairments
Confidence Intervals
Population
Pure-Tone Audiometry
Frameshift Mutation
Genetic Linkage
Nonsyndromic Deafness
Connexin 26
Middle Ear
Mutation Rate
Ethnic Groups
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Morell, R. J., Kim, H. J., Hood, L. J., Goforth, L., Friderici, K., Fisher, R., ... Dumon, J. (1998). Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness. New England Journal of Medicine, 339(21), 1500-1505. https://doi.org/10.1056/NEJM199811193392103

Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness. / Morell, Robert J.; Kim, Hung Jeff; Hood, Linda J.; Goforth, Leah; Friderici, Karen; Fisher, Rachel; Van Camp, Guy; Berlin, Charles I.; Oddoux, Carole; Ostrer, Harry; Keats, Bronya; Friedman, Thomas B.; San Agustin, Theresa; Dumon, Jan.

In: New England Journal of Medicine, Vol. 339, No. 21, 19.11.1998, p. 1500-1505.

Research output: Contribution to journalArticle

Morell, RJ, Kim, HJ, Hood, LJ, Goforth, L, Friderici, K, Fisher, R, Van Camp, G, Berlin, CI, Oddoux, C, Ostrer, H, Keats, B, Friedman, TB, San Agustin, T & Dumon, J 1998, 'Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness', New England Journal of Medicine, vol. 339, no. 21, pp. 1500-1505. https://doi.org/10.1056/NEJM199811193392103
Morell, Robert J. ; Kim, Hung Jeff ; Hood, Linda J. ; Goforth, Leah ; Friderici, Karen ; Fisher, Rachel ; Van Camp, Guy ; Berlin, Charles I. ; Oddoux, Carole ; Ostrer, Harry ; Keats, Bronya ; Friedman, Thomas B. ; San Agustin, Theresa ; Dumon, Jan. / Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness. In: New England Journal of Medicine. 1998 ; Vol. 339, No. 21. pp. 1500-1505.
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abstract = "Background. Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods. We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle- ear immittance, and recording of otoacoustic emissions. Results. Two frame- shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. Conclusions. The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations.",
author = "Morell, {Robert J.} and Kim, {Hung Jeff} and Hood, {Linda J.} and Leah Goforth and Karen Friderici and Rachel Fisher and {Van Camp}, Guy and Berlin, {Charles I.} and Carole Oddoux and Harry Ostrer and Bronya Keats and Friedman, {Thomas B.} and {San Agustin}, Theresa and Jan Dumon",
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T1 - Mutations in the connexin 26 gene (GJB2) among Ashkenazi jews with nonsyndromic recessive deafness

AU - Morell, Robert J.

AU - Kim, Hung Jeff

AU - Hood, Linda J.

AU - Goforth, Leah

AU - Friderici, Karen

AU - Fisher, Rachel

AU - Van Camp, Guy

AU - Berlin, Charles I.

AU - Oddoux, Carole

AU - Ostrer, Harry

AU - Keats, Bronya

AU - Friedman, Thomas B.

AU - San Agustin, Theresa

AU - Dumon, Jan

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N2 - Background. Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods. We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle- ear immittance, and recording of otoacoustic emissions. Results. Two frame- shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. Conclusions. The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations.

AB - Background. Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews. Methods. We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle- ear immittance, and recording of otoacoustic emissions. Results. Two frame- shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant. Conclusions. The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations.

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