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Previous Volume 339:1500-1505 November 19, 1998 Number 21 Next

	Full Text PDF Editorial by Steel, K. P. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

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.

Source Information

From the Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, Md. (R.J.M., H.J.K., T.B.F.); Kresge Hearing Research Laboratory, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans (L.J.H., L.G., C.I.B., B.K.); the Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing (K.F., R.F.); the Department of Medical Genetics, University of Antwerp, Antwerp, Belgium (G.V.C.); and the Human Genetics Program, Department of Pediatrics, New York University Medical Center, New York (C.O., H.O.). Other authors were Theresa San Agustin, M.D., Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Rockville, Md., and Jan Dumon, M.D., Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.

Address reprint requests to Dr. Morell at the NIDCD, 5 Research Ct., Rm. 2A19, Rockville, MD 20850.

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