Correspondence

Deafness and Mutations in the Connexin 26 Gene

N Engl J Med 1999; 340:1288April 22, 1999

Article

To the Editor:

Morell et al. (Nov. 19 issue)1 demonstrate that two mutations in the connexin 26 gene (GJB2) account for most of the cases of nonsyndromic recessive deafness among Ashkenazi Jews. They suggested that since the carrier rate of mutations in the GJB2 gene (4.76 percent) is similar to that of other genes governing recessive diseases in this population, such as Tay–Sachs disease, Gaucher's disease, and familial dysautonomia, Ashkenazi Jews may elect to have their carrier status determined as part of genetic screening.

Although the frequency of a disease within a population is an important factor in the decision whether to begin population screening, the first step in the decision should be to define the aim of screening. For instance, screening for phenylketonuria and hypothyroidism is done in order to allow early treatment, whereas the goal of screening for Tay–Sachs disease or thalassemia is to identify carriers and prevent these diseases. Among the genetic diseases that are relatively frequent among Ashkenazi Jews, some are very severe, such as Canavan's disease, familial dysautonomia, and mucolipidosis IV, and therefore, like Tay–Sachs disease, are candidates for population screening as a means of prevention.

With respect to deafness, screening for the relatively frequent mutations in the GJB2 gene may be appropriate, since identifying newborns who are homozygous may allow early treatment of deafness. In recent years, however, the feasibility of detecting hearing defects in newborns or other infants on the basis of either automated auditory brain-stem responses or transiently evoked otoacoustic emissions has been demonstrated; therefore, general screening of the population is possible.2,3 Such a universal approach not only would be more effective than screening for mutations, since it allows the identification of all types of hearing defects, but also would avoid the discriminative aspects associated with screening only Ashkenazi Jews.

The medical importance of the identification by Morell et al. of the specific mutations responsible for a large proportion of hearing defects in the Ashkenazi Jewish community is that it will allow the cause of the hearing defect in a child to be diagnosed relatively easily and will identify the need for genetic counseling for the family.

Joel Zlotogora, M.D., Ph.D.
Hadassah Medical School at Hebrew University, Jerusalem 91120, Israel

3 References

1. 1

   Morell RJ, Kim HJ, Hood LJ, et al. Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Engl J Med 1998;339:1500-1505
   Full Text | Web of Science | Medline

2. 2

   Bantock HM, Croxson S. Universal hearing screening using transient otoacoustic emissions in a community health clinic. Arch Dis Child 1998;78:249-253
   CrossRef | Web of Science | Medline

3. 3

   Mason JA, Herrmann KR. Universal infant hearing screening by automated auditory brainstem response measurement. Pediatrics 1998;101:221-228
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Zlotogora makes two valid points regarding the advisability of screening for GJB2 mutations in the Ashkenazi Jewish population. The first is that tests of automated auditory brain-stem responses or transiently evoked otoacoustic emissions are more appropriate ways of detecting congenital hearing impairments in newborns. Such tests would more efficiently identify congenital hearing loss at an early stage, since 50 percent of all cases have a nongenetic cause. The use of hearing tests as a screening tool also raises fewer ethical problems than does the use of genetic tests. The National Institute on Deafness and Other Communication Disorders convincingly makes the argument for universal screening based on hearing tests of newborns in a 1993 consensus statement.1

The second point is that by itself the prevalence of GJB2 mutations in a population does not justify genetic screening, in the absence of any consideration of the severity of the condition being screened for or an effective intervention for those who test positive. On this issue also we agree with him. Genetic counselors should consider testing for GJB2 carrier status if a patient so chooses. Our findings make it clear that an appropriate test for Ashkenazi Jews must be able to detect the 167delT allele in addition to the 30delG allele. However, the decision to test is an individual one, as is the decision involving what to do with the information provided by testing. We are not advocating routine screening to determine GJB2 carrier status.

Robert J. Morell, Ph.D.
Thomas B. Friedman, Ph.D.
National Institute on Deafness and Other Communication Disorders, Rockville, MD 20850

1 References

1. 1

   Early identification of hearing impairment in infants and young childrenNational Institutes of Health Development Conference Statement, March 1-3, 1993. NIH Consens Statement 1993;11:1-24
   Medline

Citing Articles (3)

Citing Articles

1. 1

   Kevin C. Harris, Christy B. Erbe, Jill B. Firszt, Valerie A. Flanary, Phillip A. Wackym. (2002) A Novel Connexin 26 Compound Heterozygous Mutation Results in Deafness. The Laryngoscope 112:7, 1159-1162
   CrossRef

2. 2

   Israela Lerer, Michal Sagi, Esther Malamud, Haya Levi, Annick Raas-Rothschild, Dvorah Abeliovich. (2000) Contribution of connexin 26 mutations to nonsyndromic deafness in Ashkenazi patients and the variable phenotypic effect of the mutation 167delT. American Journal of Medical Genetics 95:1, 53-56
   CrossRef

3. 3

   Tama Sobe, Porat Erlich, Asher Berry, Michael Korostichevsky, Sarah Vreugde, Karen B. Avraham, Batsheva Bonn-Tamir, Mordechai Shohat. (1999) High frequency of the deafness-associated 167delT mutation in the connexin 26 (GJB2) gene in Israeli Ashkenazim. American Journal of Medical Genetics 86:5, 499-500
   CrossRef