Genetic Testing For Newborn Hearing Loss
As modern technology allows rapid progress in the field of genetics, genetic testing for various disorders is becoming increasingly common. One recent development in this area is genetic testing for a form of congenital hearing loss.
Currently, newborn hearing screening programs are in place in many countries to test all infants for hearing abnormalities. However, this in itself does not produce a diagnosis for newborns who fail the tests, and indeed most of them have to wait up to three months before any diagnostic evaluation is started. This is not in the best interests of the child, as evidence shows that “identification and habilitation of deaf infants before six months of age improves language outcomes.” (Schimmenti, et al., 2011)
Figure 1. Infant undergoing hearing screening
(Preserving the Future of Newborn Screening, 2011)
Almost half of all infants with congenital hearing loss have underlying genetic causes for their condition. It has recently been identified that the most prevalent of these are mutations of the Gap Junction Beta-2 gene (GJB2). (Schimmenti, et al., 2011) GJB2 is responsible for directing the synthesis of Connexin 26, a protein that helps to create gap junctions in the cochlea through which potassium ions can flow, thus having an important role in the homeostatic regulation of potassium in this area. This process is essential for maintaining appropriate levels of potassium in the inner ear and thus preventing the malfunction and damage of cells vital for hearing. Connexion 26 may also play an important role in the maturation of certain cochlear cells. More than 90 mutations of the GJB2 gene have been identified thus far that produce a non-functional Connexin 26 protein and result in congenital hearing loss. (Palmer & Boudreault)
Figure 2. Half of all newborn deafness is the result of genetic causes
(National Deaf Children’s Society, 2008)
All of these mutations studied to date are autosomal recessively inherited, however it is known that autosomal dominant mutations also exist. Of the afore-mentioned mutations, the majority exert their effects by deleting base pairs. This changes the sequence of amino acids produced and leads to the manufacture of a misshapen and unstable Connexin 26 protein.
Fortunately, a genetic test for the most common of these base pair deletion mutations has recently been derived. Blood samples can be taken from newborns and the appropriate segment of DNA isolated and amplified through PCR then sequenced using this genetic test to determine if the mutation is present. This test has been experimentally proven to detect the majority of infants with GJB2-related hearing loss amongst those that fail hearing screening tests. (Schimmenti, et al., 2011)
Schimmenti et al. (2011) believe that these genetic testing results could be available before traditional diagnostic testing begins and so would lead to an earlier diagnosis and therefore better speech and learning outcomes for many individuals. It is also anticipated that further genetic testing for many other hearing loss-associated mutations of this gene will become available in the near future. Considering that GJB2-related hearing loss is accountable for the majority of genetic hearing loss (and genetic conditions cause half of all deafness), undertaking genetic testing for mutations in this gene may therefore be very worthwhile. This process would involve taking a small blood sample from newborns who fail the hearing screening tests and analysing it for the presence of a mutated GBJ2 gene.
Deaf Children’s Society 2008, The Genetics of Hearing Loss, viewed 20 March 2012, <http://www.aussiedeafkids.org.au/the-genetics-of-hearing-loss-1.html>
Palmer, C & Boudreault, P n.d., Deaf Genetics Project, viewed 18 March 2012, <http://www.deafgeneticsproject.org/conexin%2026.html>
Preserving the Future of Newborn Screening 2011, What is Newborn Screening?, viewed 20 March 2012, <http://www.newbornbloodspots.org/index.php/learn_more/what_is_newborn_screening/>
Schimmenti, LA, Warman, B, Schleiss, M, Daly, KA, Ross, JA, McCann, M et al. 2011, ‘Evaluation of newborn screening bloodspot-based genetic testing as second tier screen for bedside newborn hearing screening’, Genetics in Medicine, pp. 1006-1010