Deafness, Autosomal Dominant 3A (DFNA3A) and Deafness, Autosomal Recessive 1A (DFNB1A) via the GJB2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7677 GJB2 81252 81252,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7677GJB281252 81252(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hereditary or familial hearing loss (HL) and deafness can be prelingual (before language develops) or postlingual (after language develops) and may be conductive, sensorineural, or a combination of both. Causes for hereditary HL can be syndromic (associated with malformations of the external ear or other organs or with medical problems involving other organ systems) or nonsyndromic (no associated visible abnormalities of the external ear or any related medical problems). Familial forms of hearing loss must be distinguished from acquired (non-genetic) causes of hearing loss (such as environmental effects or mechanical stress) and are diagnosed by otologic, audiologic, and physical examination, family history, ancillary testing (e.g., CT examination of the temporal bone), and molecular genetic testing. Molecular genetic testing is possible for many types of syndromic and nonsyndromic deafness and plays a prominent role in diagnosis and genetic counseling (Smith et al, 2013).

Nonsyndromic hearing loss and deafness is characterized by childhood-onset, progressive, moderate-to-severe high-frequency sensorineural hearing impairment. The audioprofile may vary significantly, even among family members. Affected individuals have no other associated medical findings (Smith et al, 2013).

Genetics

Nonsyndromic hearing loss and deafness via GJB2 exhibits two modes of inheritance. The different gene loci for nonsyndromic hearing loss are designated DFN (for DeaFNess) and named on the mode of inheritance; DFNA for autosomal dominant, DFNB for autosomal recessive and DFNX for X-linked inheritance respectively. GJB2 mediated deafness and hearing loss are inherited in both autosomal dominant (DFNA3A) and autosomal recessive (DFNB1A) modes.

The GJB2 gene codes for the gap junction beta 2 protein, more commonly known as connexin 26. Connexins form gap junctions that permit the transport of nutrients, charged atoms (ions), and signaling molecules between neighboring cells that are in contact with each other. Connexin 26 transports potassium ions and certain small molecules. GJB2 gene mutations probably alter gap junctions, which may disturb the level of potassium ions in the inner ear. Levels of potassium ions that are too high may affect the function and survival of cells that are needed for hearing. Connexin 26 also plays a role in the growth, maturation, and stability of the outermost layer of skin (the epidermis).

Mutations in GJB2 account for >90% of all DFNA3 cases and ~98% of DFNB1 cases. Mutations include single nucleotide deletions and missense variants. Mutations in GJB6 (Connexin 30) account for the remaining cases of DFNA3 and DFNB1.

Clinical Sensitivity - Sequencing with CNV PG-Select

GJB2 mutations account for 60-70% of nonsyndromic hearing loss cases (Smith et al, 2013). The most common mutations in GJB2 are single nucleotide deletions, c.35delG in particular. Our sequencing assay is able to detect >90% of mutations associated with this gene.

Testing Strategy

This test provides full coverage of all coding exons of the GJB2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Nonsyndromic hearing loss and deafness, DFNA3, is suspected in individuals with the following: pre- or postlingual, mild to profound, progressive sensorineural hearing impairment; no related systemic findings identified by medical history and physical examination; or a family history of nonsyndromic hearing loss consistent with autosomal dominant inheritance.

GJB2 testing should be considered in neonates with confirmed hearing loss if familial and nonsyndromic hearing loss is suspected (ACMG guidelines 2009, seen in Smith, 2013).

This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GJB2.

Gene

Official Gene Symbol OMIM ID
GJB2 121011
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Smith JH, Shearer AE, Hildebrand MS, Van Camp G. 2013. Deafness and Hereditary Hearing Loss Overview. GeneReviews. PubMed ID: 20301607

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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