In the United States, approximately 1 in 1000 children are diagnosed with prelingual hearing loss (HL) or deafness. Approximately half of prelingual hearing loss or deafness is attributed to environmental exposures and the remaining half is attributed to genetic causes. Approximately 30% of hereditary hearing loss is estimated to be syndromic (associated with other birth defects) while the remaining 70% is non-syndromic (isolated and not associated with other findings). Non-syndromic deafness is mainly due to recessive genes (75-80%) and over 20 such genes have been identified, but non-syndromic deafness may also be inherited in autosomal dominant, X-linked, or mitochondrial patterns.
Molecular testing can aid in rapid diagnosis of hearing loss. Early diagnosis of hearing defects can provide diagnostic information, facilitate timely intervention, and assist with genetic counseling.
Connexins are transmembrane proteins that form channels that allow rapid transport of small molecules between cells; the proteins connexin 26 and connexin 30 interact to form a channel that functions in the inner ear. The GJB2 gene encodes the connexin 26 protein and is involved in 50% of autosomal recessive hearing loss. The GJB6 gene is located near the GJB2 gene, and encodes the protein connexin 30. Patients with non-syndromic hearing loss have been found to have two mutations in connexin 26, two mutations in connexin 30, or compound heterozygosity for one mutation in connexin 26 and one mutation in connexin 30 [1,2].
This test involves sequencing of the entire coding sequence of the GJB2 gene that encodes the connexin 26 protein.
- GeneReviews Clinical Summary
- Pandya A, et al. (2003) Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Genet Med 5:295-303.
- Del Castillo I, et al. (2003). Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am J Hum Genet 73:1452-8.
- Individuals with clinical findings consistent with non-syndromic hearing loss when mitochondrial etiologies have been ruled out and testing of connexin 30 has resulted in no mutations found or one mutation found.
Orangene™ Saliva Collection Kit used according to manufacturer instructions. Please contact EGL for a Saliva Collection Kit for patients that cannot provide a blood sample.
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
- The Hearing Loss Panel (HL) is indicated for patients who have not have previous molecular testing and includes sequencing of the GJB2 and GJB6 genes, targeted mutation analysis of the GJB6 common 342kb deletion, and testing for mitochondrial mutations associated with aminoglycoside sensitivity.
- For patients with mutations not identified by full gene sequencing, a separate Deletion/Duplication Assay is available for connexin 26 and connexin 30 using a targeted CGH array. Refer to the test requisition or contact the laboratory for more information.
- Custom Diagnostic Mutation Analysis (KM) is available to family members if mutations are identified by sequencing.
- Prenatal testing is available to couples who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.
- Mitochondrial Mutation Panel for patients with a history of aminoglycoside sensitivity (QJ)
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