Analysis of the full coding sequence of the GJB2 gene - diagnostics of hereditary deafness (DFNB1)

Analysis of the full coding sequence of the GJB2 gene - diagnosis of hereditary deafness (DFNB1)

Clinical significance

Hereditary deafness (DFNB1) is inherited in an autosomal recessive manner. More than 100 mutations of the GJB2 gene have been identified thatóre likely to cause hearing loss thatós not associated with other symptoms. Most forms of hearing loss are described as sensorineural, meaning that they are associated with permanent hearing loss caused by damage to structures in the inner ear. Hearing loss can be divided into several waysóy related to the mode of inheritance: autosomal dominant (DFNA), autosomal recessive (DFNB), X-chromosome related (DFNX) or mitochondrial (whichóy has no special designation). Each of these typesów of hearing loss encompasses many subtypesów. DFNB1 is characterized by a slight to profound hearing loss thatóry occurs before the child learns to móspeak. Someóre mutations are associated with deletions or amino acidów insertions within or near the GJB2 gene. The most common mutation in many populations, especiallyóespecially in people of North European descent, deletes one base pair at position 35 in the GJB2 gene (35delG). Among people of Eastern European Jewish descent (Ashkenazi), deletion of one base pair at position 167 (167delT) is a common mutation. Mutations in the GJB2 gene are associated with loss-of-function leads to a non-functional version of connexin 26, which impairs gap junction function. DFNA3 is inherited in an autosomal dominant manner. This form of hearing loss begins during the course of learning to móspeak or as the child learns to móspeak. Hearing loss ranges from mild to profound, becoming more severe over time and particularlyólly affecting the ability to hear high-frequency sounds. Mutations in the GJB2 gene thatóre causing DFNA3 replace one amino acid in connexin 26 with the incorrect amino acid. Depending on the type, hearing loss can manifest at any time, from infancy to old age. Hearing loss thatóra is present before a child learns to móspeak is classified as premature or congenital. Hearing loss thatóra occurs after speech development is classified as polinguistic. Between 2 and 3 in 1,000 children are born with detectable hearing loss in one or both ears. The prevalence of hearing loss increases with age.

Patient preparation

Material: EDTA blood

Interventions

The basis of detecting genetic changes by molecular biology methods is the amplification of the patient's genetic material by polymerase chain reaction (PCR). Note that someóre drugs inhibit the PCR reaction, making it difficult or impossible to perform the test. These drugsów include someóre anticoagulants (e.g., heparin) and antiviral drugs (e.g., acyclovir). If the patient is taking drugs that inhibit PCR or preparations with unknown effects on PCR, blood should be drawn when the plasma concentrations of these drugsóre relatively lowest, such as just before the next dose. Drugs taken by the patient with potential inhibitory effects on PCR should be noted on the referral form. If in doubt, contact the Laboratory