Hearing Loss, Nonsyndromic Panel (GJB2) Sequencing, (GJB6) 2 Deletions and Mitochondrial DNA 2 Mutations
2001992
 
Ordering Recommendation
Diagnostic testing for nonsyndromic hearing loss.
Mnemonic
HL PANEL
Methodology
Polymerase Chain Reaction/Capillary Electrophoresis/Sequencing
Performed
Varies
Reported
Within 21 days
New York DOH Approval Status
Specimens from New York clients will be sent out to a New York DOH approved laboratory.
Specimen Required
Patient Preparation
 
Collect
Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).  
Specimen Preparation
Transport 3 mL whole blood. (Min: 2 mL)  
Storage/Transport Temperature
Refrigerated.  
Unacceptable Conditions
 
Remarks
 
Stability
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable  
Reference Interval
By report
Interpretive Data
Background Information for Hearing Loss, Nonsyndromic Panel (GJB2) Sequencing, (GJB6) 2 Deletions and Mitochondrial DNA 2 Mutations:
Characteristics
: Nonsyndromic hearing loss (NSHL).
Incidence
: Approximately 1 in 2600 for NSHL; 50 percent due to GJB2 mutations, 2-4 percent associated with GJB6 deletions, and 1-2 percent related to
mitochondrial mutations.
Inheritance:
Dependent on gene. GJB2: Autosomal recessive; rarely dominant. GJB6: Autosomal recessive; resulting from either two GJB6 deletions or one GJB6 deletion and one GJB2 mutation on the opposite chromosome. Mitochondrial DNA: Dominant maternal inheritance.
Penetrance:
Complete for GJB6; variable for GJB2 and mitochondrial DNA.
Cause:
Deleterious GJB2, GJB6, and mitochondrial DNA mutations.
Mutations Tested:
GJB2: Coding region, intron-exon boundary and 5'-UTR mutations. GJB6: 309kb del(GJB6-D13S1830), previously reported as 342kb, and 232kb del(GJB6-D13S1854). Mitochondrial: m.1555A>G and m.7445A>G.
Clinical Sensitivity
: 50-55 percent for Caucasians with NSHL; unknown in other ethnicities.
Methodology for GJB2 Sequencing:
Bidirectional sequencing of the entire coding region, intron-exon boundaries, and 5'-UTR of the GJB2 gene.
Methodology for GJB6 2 Deletions
: Multiplex PCR using deletion-specific primers followed by capillary gel electrophoresis.
Methodology for Mitochondrial DNA 2 Mutations:
Targeted bidirectional sequencing of mitochondrial mt-RNR1 m.1555A>G and mt-TS1 m.7445A>G.
Analytical Sensitivity and Specificity
: Greater than 99 percent.
Limitations
: Diagnostic errors can occur due to rare sequence variations. GJB2 regulatory region mutations, deep intronic mutations and large deletions or duplications will not be detected. GJB6 and mitochondrial DNA mutations, aside from those targeted will not be detected. The etiology of hearing loss due to other genetic or environmental causes will not be determined.



Counseling and informed consent are recommended for genetic testing. Consent forms are available online at www.aruplab.com.

See Compliance Statement C: www.aruplab.com/CS
Note
CPT Code(s)
81252, 81254, 81401
Components
Component Test Code*Component Chart Name
2001993Mitochondrial DNA, 2 Mutations
2001994Hearing Loss Panel Interpretation
2001996Connexin 30 GJB6 Deletions
2001997GJB2 Sequencing
2001998HL Panel Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, contact interface support at interface.support@aruplab.com.
Cross References
  • Deafness (Hearing Loss, Nonsyndromic Panel (GJB2) Sequencing, (GJB6) 2 Deletions and Mitochondrial DNA 2 Mutations)
  • GJB6 (Hearing Loss, Nonsyndromic Panel (GJB2) Sequencing, (GJB6) 2 Deletions and Mitochondrial DNA 2 Mutations)
  • Hearing Loss (Hearing Loss, Nonsyndromic Panel (GJB2) Sequencing, (GJB6) 2 Deletions and Mitochondrial DNA 2 Mutations)