- Patient Preparation
- Lavender (EDTA), pink (K2EDTA), or yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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
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 ofthe entire coding region, intron-exon boundaries, and 5'-UTR of the GJB2gene.
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.
|Component Test Code*||Component Chart Name||LOINC|
|2001993||Mitochondrial DNA, 2 Mutations|
|2001994||Hearing Loss Panel Interpretation|
|2001996||Connexin 30 GJB6 Deletions|
|2001998||HL Panel Specimen|
- Connexin 26 mutation assay
- GJB2 sequencing, del/dup
- mtDNA, Connexin 30, Connexin 26 mutation assay