Connexin 26, a protein that is critical for normal cochlear function, is encoded by the gene GJB2. A single mutation of this gene is responsible for approximately 50% of all cases of inherited, congenital severe-to-profound nonsyndromic hearing loss. Genetic testing can identify the presence of the mutation. A brief summary is presented on what hearing care professionals should know about the GJB2 and its implications for genetic counseling.

Severe to profound sensorineural hearing loss occurs in 1-in-1000 newborns. In about half the cases, the cause is genetic. In cases of inherited hearing loss, about 70% are nonsyndromic, and about 75% are autosomal recessive.

In a paper published in the American Journal of Audiology, McGuirt & Smith presented findings from a number of studies on inherited hearing loss.1 According to the authors, nearly 60 loci of deafness-causing genes are believed to exist, although only a relatively few sites have been identified.

One of the genes that has been identified makes a major contribution to the genetic load for autosomal recessive nonsyndromic hearing loss. The gene, GJB2 (gap-junction beta 2), encodes the protein Connexin 26 (Cx26). Normal function of this protein is required to maintain the high potassium concentration within the scala media of the cochlea.

Mutations in the GJB2 gene disrupt production of Cx26, typically resulting in nonsyndromic severe to profound congenital sensorineural hearing loss. In many (but not all) populations, almost all cases are due to a single mutation that results in the loss of a guanosine nucleotide. Thus, a single mutation in GJB2 leads to disruption of Cx26 and is “the cause of up to 50% of hereditary pre-lingual severe-to-profound nonsyndromic hearing loss.” In the midwestern United States, 2.5% of the population are carriers for the mutation.

Genetic Testing and Counseling
Genetic testing for Cx26 is available in several laboratories in the United States. Such testing may be warranted in cases of patients with pre-lingual severe-to-profound sensorineural hearing loss of unknown etiology. Genetic test results may:

1) Be reassuring to concerned families;
2) Facilitate early habilitation; and
3) Facilitate genetic counseling.

Case Report

A white male with severe congenital sensorineural hearing loss and his wife, a white female with normal hearing, received genetic testing and counseling. Results indicated the man had a Cx26 mutation; his wife had no Cx26 variants.

The genetic test results suggest that the chances of this couple having a child with severe to profound hearing loss are very low. However, all their offspring will be carriers of Cx26 mutations (inherited from the father).

People referred for Cx26 genetic testing have no family history of hearing loss. The parents should understand that if both parents are carriers, there is a 25% chance that each future offspring will have hearing loss. There is a 66% chance that their normal-hearing children will be carriers themselves.

According to McGuirt & Smith, because 50% of all pre-lingual severe-to-profound hearing losses are Cx26-related and caused by a single mutation of the GJB2 gene, genetic testing is highly specific. If such testing is done, it is critical that appropriate counseling is provided so the results and implications of the genetic testing are understood.

This research update was provided by Dennis Hampton, PhD, editor of Hearing HealthCare News and Audiology HealthCare News, White Plains, NY. The article is adapted from an article that appeared in the latter. Correspondence can be addressed to HR or Dennis Hampton, PhD, Hearing HealthCare News, 280 Mamaroneck Ave, Ste. 204, White Plains, NY 10605; email: [email protected].

1. McGuirt W & Smith R: Connexin as a cause of hereditary hearing loss. Amer J of Audiol 1999; 8: 93-100.