Deafness can be caused, in addition to acoustic trauma, ototoxic drugs and infections duringpregnancy or after birth, also by genetic factors. Half of the cases of childish deafness has a genetic origin, and it is evaluated that 1 child on 1000 has at birth problems or hearing defect . The genetic deafness can be divided into two groups:
• not-syndromic forms where hearing loss is not combined to other symptoms and they include about 70% of cases. Two thirds of these forms has a recessive autosomal transmission, one third has an dominant autosomal transmission, while only 1-2% has a transmission associated with the X chromosome. A not yet defined percentage is caused by mitochondrial DNA mutations.
• syndromic forms in which hearing loss is combined with other clinical conditions and they include the remaining 30% of cases. The most common syndromic forms are Pendred syndrome (deafness and goiter) and Usher syndrome (a gradual blindness and deafness).
In the most of cases (about 80%) of genetic not-syndromic deafness wit a recessive autosomal transmission is involved the connexin 26 gene (Cx26, also known as GJB2, gap-junction protein beta 2). Alterations of this gene are numerous, but the most frequent
mutation (50-80% of cases) is known as 30/35delG. The frequency of healthy carriers (asymptomatics) in Italy is of 1 to 35 individuals. Two healthy carriers parents (asymptomatic) will have a 25% probability of having children with not syndromic genetic deafness. Themselves will have children with 50% probability of being healthy carriers, as their parents. The Cx26 gene encodes for connexin 26, a protein forms junction channels to put in communication cochlear cells and to allow the passage of chemical mediators, including potassium ion, foundamental to the ear function. Another mutation of the GJB2 gene, less frequent of 30/35delG, is the 167delT.
Another gene associated with not syndromic deafness is Cx30 or GJB6 (gap-junction protein beta 6) encoding connexin 30. Published studies have shown the presence of a mutation (D13S1830) ,a deletion within the gene. Deletion of GJB6, in homozygous (both copies of the gene are mutated) or associated with a mutation in the gene Cx26 (compound heterozygous) cause hearing loss.
Genetic test allows to search a 35delG and 167delT mutation of connexin 26 gene that are about 90% of the mutations present in the Italian population. The test keep out even the most frequent mutation (D13S1830) of gene of the connexin 30.
For example, as a result of molecular analysis to search one of these mutations, it can get three kind of results:
• one copy of the gene Cx26 is mutated, while the other copy is normal. So an individual is heterozygous for the mutation, and he is a healthy carrier, asymptomatic.
• both copies of the gene Cx26 are mutated. so an individual is homozygous for the mutation and he is affected by not syndromic genetic deafness.
• Absence of a mutation in the gene Cx26. This "negative" result for mutations means that an individual has a reduced possibility to be a carrier. The first level genetic test not reset the chance of being a carrier, because it isn’t possible to exclude the presence of other gene Cx26 mutations (in case of negative result the residual risk is about 1 on 350).
Tecnobios Prenatale Eurogenlab laboratory, gives a genetic counseling service to inform patients and parents, in a clear terms about the risk of disease transmission within the family, on the possibilities of diagnosis and pre-and postnatal treatment.
The result of the analysis for research of the principal mutation is available after 10 days from the draw blood.
DNA extracted from peripheral blood lymphocytes (in tubes with EDTA), chorionic villi, amniotic fluid.
Malattie genetiche – Cao, Dalla Piccola, Notarangelo – Piccin (2004)
D'Andrea P et al - Biochem Biophys Res (2002)
Del Castillo I et al. - New Eng. J. Med (2002)