Diagnostic test for individuals with nonsyndromic hearing loss and 1 identified GJB2 variant. Carrier screening if family history of GJB6 deletion or for reproductive partner of individual with GJB6 or GJB2 variants.
Polymerase Chain Reaction/Capillary Electrophoresis
New York DOH Approval Status
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Refrigerated. Also acceptable: Room temperature
Ambient: 1 week; Refrigerated: 1 month; Frozen: Unacceptable
Background: Hearing Loss, Nonsyndromic, Connexin 30 (GJB6) 2 Deletions:
Characteristics: Moderate to profound nonsyndromic hearing loss (NSHL). Large GJB6 gene deletions involving cis-regulatory elements for GJB2 (connexin 26) result in the loss of expression of GJB2. Thus, compound heterozygosity for a pathogenic GJB2 variant and GJB6 large deletion results in NSHL.
Incidence: Approximately 1 in 30 individuals with NSHL has a GJB6 deletion; 1 in 100,000 in the general population. Twenty percent of GJB2 heterozygotes with nonsyndromic hearing loss have a GJB6 deletion; homozygosity for GJB6 deletions is rare.
Inheritance: Autosomal recessive.
Cause: Pathogenic germline variants in GJB6.
Variants Tested: 309kb del(GJB6-D13S1830, also known as 342kb) and 232kb del(GJB6-D13S1854).
Clinical Sensitivity: Dependent on ethnicity.
Methodology: Multiplex PCR using deletion-specific primers, followed by capillary gel electrophoresis.
Analytical Sensitivity and Specificity: Greater than 99 percent.
Limitations: GJB6 variants other than the two targeted deletions will not be identified. The etiology of hearing loss due to other genetic or environmental causes will not be determined. Diagnostic errors can occur due to rare sequence variations. Interpretation of this test result may be impacted if this patient has had an allogeneic stem cell transplantation.
This test was developed and its performance characteristics determined by ARUP Laboratories. It has not been cleared or approved by the US Food and Drug Administration. This test was performed in a CLIA certified laboratory and is intended for clinical purposes.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2001957||Connexin 30 GJB6 Deletion 309||34504-1|
|2001958||GJB6 DEL Specimen Type||31208-2|
|2001959||Connexin 30 Interpretation||50398-7|
|2002107||Connexin 30 GJB6 Deletion 232||41100-9|
- Connexin 30 mutation assay
- GJB6 deletions assay