Genetic hearing loss gene panel (GJB2, SLC26A4)

Diagnostic Use

Testing comprises targeted sequence analysis of the GJB2 and SLC26A4 genes, as well as detection of the large deletions involving the GJB6 gene (del(GJB6-D13S1830), del(GJB6-D13S1854)) which result in loss of cis acting regulatory elements essential for GJB2 expression.

Biallelic pathogenic variants in GJB2 are the leading cause of autosomal recessive non-syndromic sensorineural hearing loss. They account for approximately 15–25% of all congenital hearing loss in many populations and up to 50% of autosomal recessive non-syndromic cases, with detection rates influenced by ancestry and founder variants. GJB2-related hearing loss is typically congenital, bilateral, and non-syndromic. Identification of causative variants provides a definitive molecular diagnosis, clarifies recurrence risk (25% for carrier parents), and may reduce the need for additional diagnostic investigations.

Pathogenic variants in SLC26A4 are the second most common cause of autosomal recessive hearing loss in several populations. They are detected in approximately 5–10% of individuals with congenital or early-onset hearing loss overall, and in up to 30–50% of patients with enlarged vestibular aqueduct (EVA). Biallelic variants are associated with Pendred syndrome and non-syndromic EVA-related hearing loss, which may be congenital, progressive, or fluctuating. Molecular confirmation supports appropriate clinical management, including thyroid surveillance where indicated, and provides important prognostic information.

For more information, see GeneReviews www.ncbi.nlm.nih.gov/books/NBK1434/

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

Connexin 26 Gene Analysis
DFNB1 sequencing
GJB2 sequencing
GJB6 sequencing
SLC26A4 sequencing

Turnaround Time

4 weeks

Test Code

4193

Specimen Type

• Whole Blood
• DNA extract

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.

An aliquot of DNA extracted by another accredited diagnostic laboratory is also an acceptable sample type. DNA extracts should be at least 20uL of DNA at a concentration no less than 20ng/uL. Please contact the laboratory to discuss specific requirements if the available DNA does not meet these standards.

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.

Reference Intervals

Sequence variants plus single/multi exon deletions and duplications (aka copy number variants (CNVs) are detected by this method. The large deletions involving GJB6 (del(GJB6-D13S1830), 309kb and del(GJB6-D13S1854), 131kb) are also detected.

Test Method

Testing is by targeted NGS gene panel analysis of the GJB2 (NM_004004.5) and SLC26A4 (NM_000441.2) genes. Detection of the del(GJB6-D13S1830) and del(GJB6-D13S1854) deletions is by copy number analysis of the GJB6 and CRYL1 genes, and confirmation by gap-PCR.

Contact Canterbury Health Laboratories on +64 3 364 0484 or email LabInfo@cdhb.health.nz

Uncertainty of Measurement:
Targeted NGS DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Contact Information

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