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Connexin 26

What is Connexin 26?

Connexin 26 (Cx26) is a protein found on the (GJB2) gene and is the most common cause of congenital sensorineural hearing loss. Connexin 26 mutations are responsible for at least 20% of all genetic hearing loss and 10% of all childhood hearing loss. In some ethnic populations, more than 80 percent of cases of nonsyndromic recessive deafness result from a mutated Connexin 26 gene. Children born with bilateral (both ears) severe to profound sensorineural hearing losses are typically referred for genetic testing for Connexin 26 mutations.

Connexin 26 mutations are genetically transmitted from parent to child in a recessive manner, which means that an affected individual must inherit one copy of the non-functioning gene from each parent. Carriers who only have one copy of the gene (i.e. one normal gene and one mutated gene) do not manifest any of the signs of the condition, but have a 1 in 2 chance of passing on the defective gene to their children (who would then also be carriers only), and a 1 in 4 chance of having an affected child if the other parent is also a carrier.

Connexin 26 mutations are non-syndromic, meaning that the mutation produces only isolated hearing loss. There is NO increased risk for other medical problems that are commonly associated with hearing loss such as blindness, thyroid problems, kidney problems, or balance disorders. However, there is in a minority of cases a higher incidence of skin disorders in patients with a Connexin 26 mutation.

Connexin 26 mutations produce a pre-lingual hearing loss, because it affects the child before they are old enough to develop speech.

Recent medical evidence has shown that there is an additional complexity to Connexin 26 mutations. Currently, only about 75% of the mutations predicted to be Cx26 actually show up in genetic testing. In some cases this may be due to mutations in another gene immediately adjacent to Cx26 called Connexin 30 (Cx30) at gene (GJB6). Connexin 26 and Connexin 30 are expressed in the same hair cells of the cochlea. Cx26 and Cx30 are similar, sharing over three-quarters of the same amino acid sequences. These considerations have led researchers to believe that mutations in Cx30 are probably also responsible for hearing loss.

Why do we need Connexin 26 to hear?

The GJB2 gene contains the instructions for manufacturing a number of proteins, including Connexin 26. Connexin proteins in general are called “gap-junction proteins” which are necessary for cells to communicate with each other. Without sufficient levels of Connexin 26, the potassium flow from hair cells in the cochlea is disrupted, resulting in extremely high levels of potassium in the Corti s organ, leading to the profound sensorineural hearing loss.

Connexin 26 mutations occur primarily in Caucasians, Ashkenazi Jews, and some Asian populations.

Treatment

A specialized interdisciplinary team of professionals is necessary to treat all of the issues associated with a Connexin 26 mutation. This group of individuals should include an Otologist or Otolaryngologists, audiologists, speech-language pathologists, a clinical geneticist and a genetic counselor. All of these individuals should have extensive experience in pediatrics.

The California Ear Institute is a leading global center for otological, otolaryngological and audiological treatment. Dr. Joseph Roberson, a board certified neurotologist, has performed thousands of successful hearing related surgeries on children and adults, including many whose hearing impairment is due to a Connexin mutation.

 

Consequences of Avoiding Treatment

If it is the desire of the family for their child to hear and speak as normally as possible, it is necessary to seek medical evaluation as soon as possible after birth of a child who is referred by their newborn hearing screening program for additional testing, regardless of whether or not Connexin 26 is suspected to be the source of the hearing loss. Delays in treatment for profound sensorineural hearing loss will result in the inability for the patient to develop normal spoken speech and language skills. Additionally, candidacy for cochlear implantation, currently the only medical treatment available for the treatment of profound sensorineural hearing loss, cannot be established without a comprehensive medical examination. Avoiding medical evaluation for a Connexin 26 mutation or any other hearing impairment related disorder is not recommended.

Additional Notes

Patients searching the internet for information about Connexin 26 mutation or any other medical issue should know when reading about individual case histories, that generally it is the patients with the most severe symptoms who either post their own experiences or are included in medical review journals. As a result, it is easy to become overly alarmed and assume the worst. Patients should keep this in mind as they explore the available resources, and look for sources that are certified by HON or other reputable health reviewing organizations. As with all medical conditions, prompt treatment by experienced medical personnel give the best chance for a positive outcome.

Additional Reading

  1. Gopalarao D, Kimberling WJ, Jesteadt W, Kelley PM, Beauchaine KL, Cohn ES. Is hearing loss due to mutations in the Connexin 26 gene progressive? Int J Audiol. 2008 Jan;47(1):11-20.
  2. Welsh LW, Welsh JJ. Re: Pediatric otolaryngologists' use of genetic testing. Ann Otol Rhinol Laryngol. 2007 Aug;116(8):637-8. No abstract available.
  3. Putcha GV, Bejjani BA, Bleoo S, Booker JK, Carey JC, Carson N, Das S, Dempsey MA, Gastier-Foster JM, Greinwald JH Jr, Hoffmann ML, Jeng LJ, Kenna MA, Khababa I, Lilley M, Mao R, Muralidharan K, Otani IM, Rehm HL, Schaefer F, Seltzer WK, Spector EB, Springer MA, Weck KE, Wenstrup RJ, Withrow S, Wu BL, Zariwala MA, Schrijver I. A multicenter study of the frequency and distribution of GJB2 and GJB6 mutations in a large North American cohort. Genet Med. 2007 Jul;9(7):413-26.
  4. Matos T, Caria H, Teixeira H, Fialho G. Gene symbol: GJB2. Hum Genet. 2007 Apr;121(2):298.
  5. Leshinsky-Silver E, Berman Z, Vinkler C, Yannov-Sharav M, Lev D. Gene symbol: GJB2. Hum Genet. 2007 Apr;121(2):296.
  6. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1279509
  7. http://deafness.about.com/od/diseasesandsyndromes/a/connexin26.htm
  8. http://www.ncbi.nlm.nih.gov/disease/deafness.html

 

 

 

 


 
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