GJB2/GJB6 - Clinical Genetic Test - GTR

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GJB2/GJB6

Clinical Genetic Test

offered by

Molecular Otolaryngology and Renal Research Laboratories

View lab's test page

GTR Test Accession: GTR000562143.5

INHERITED DISEASEEAR, NOSE, THROATCONNECTIVE TISSUE ... View more

Last updated in GTR: 2024-01-10

Last annual review date for the lab: 2024-01-11

At a Glance

Test purpose:

Diagnosis; Mutation Confirmation

Conditions (5):

Autosomal recessive nonsyndromic hearing loss 1A; Autosomal dominant keratitis-ichthyosis-hearing loss syndrome; Autosomal dominant nonsyndromic hearing loss; ...

Genes (2):

GJB2 (13q12.11), GJB6 (13q12.11)

Methods (2):

Molecular Genetics - Deletion/duplication analysis: Multiplex PCR using deletion-specific primers followed by gel electrophoresis; ...

Target population:

Not provided

Clinical validity:

Not provided

Clinical utility:

Establish or confirm diagnosis

Ordering Information

Offered by:

Molecular Otolaryngology and Renal Research Laboratories
View lab's website
View lab's test page

Test short name:

DFNB1

Specimen Source:

Buccal swab
Isolated DNA
Peripheral (whole) blood
Saliva
View specimen requirements

Who can order:

Genetic Counselor
Health Care Provider
Licensed Physician
Nurse Practitioner
Physician Assistant

Test Order Code:

GJB2/GJB6
View other test codes

CPT codes:

81252
81254

**AMA CPT codes notice

Lab contact:

Amy Weaver, Administrator
amy-weaver@uiowa.edu
319-335-6623
Jori Hendon, BA, Administrator
jori-hendon@uiowa.edu
319-335-6653

Contact Policy:

Laboratory can only accept contact from health care providers. Patients/families are encouraged to discuss genetic testing options with their health care provider.

How to Order:

Sample types accepted include: 3-5 cc EDTA whole blood; 5 μg DNA, resuspended in at least 50 ul of DNA Elution Buffer; Saliva (DNA Genotek, ORAGene Discover, OGR-500); or Buccal Swabs, at least 4 (DNA Genotek, OraCollect, OCD-100). Samples can be received Monday - Friday (no weekend or holiday deliveries), …

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Order URL

Test service:

Clinical Testing/Confirmation of Mutations Identified Previously

Test additional service:

Custom mutation-specific/Carrier testing

Test development:

Test developed by laboratory (no manufacturer test name)

Informed consent required:

Based on applicable state law

Test strategy:

GJB2 variant screening is performed by amplification of oligonucleotide primers that flank each exon followed by bi-directional sequencing. Screening for the del(GJB6-D13S1830) and del(GJB6-D13S1854) variants is completed by PCR amplification of oligonucleotide primers flanking and within the deletion breakpoints. Products are run on agarose gel and sized to determine presence … View more

View citations (6)

A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. del Castillo I, et al. N Engl J Med. 2002;346(4):243-9. doi:10.1056/NEJMoa012052. PMID: 11807148.
Del Castillo I, Moreno-Pelayo MA, Del Castillo FJ, Brownstein Z, Marlin S, Adina Q, Cockburn DJ, Pandya A, Siemering KR, Chamberlin GP, Ballana E, Wuyts W, Maciel-Guerra AT, Alvarez A, Villamar M, Shohat M, Abeliovich D, Dahl HH, Estivill X, Gasparini P, Hutchin T, Nance WE, Sartorato EL, Smith RJ, Van Camp G, Avraham KB, Petit C, Moreno F. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am J Hum Genet. 2003;73(6):1452-8. doi:10.1086/380205. Epub 2003 Oct 21. PMID: 14571368.
GJB2: the spectrum of deafness-causing allele variants and their phenotype. Azaiez H, et al. Hum Mutat. 2004;24(4):305-11. doi:10.1002/humu.20084. PMID: 15365987.
A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. del Castillo FJ, et al. J Med Genet. 2005;42(7):588-94. doi:10.1136/jmg.2004.028324. PMID: 15994881.
Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J, Mueller-Malesinska M, Pollak A, Ploski R, Murgia A, Orzan E, Castorina P, Ambrosetti U, Nowakowska-Szyrwinska E, Bal J, Wiszniewski W, Janecke AR, Nekahm-Heis D, Seeman P, Bendova O, Kenna MA, Frangulov A, Rehm HL, Tekin M, Incesulu A, Dahl HH, du Sart D, Jenkins L, Lucas D, Bitner-Glindzicz M, Avraham KB, Brownstein Z, del Castillo I, Moreno F, Blin N, Pfister M, Sziklai I, Toth T, Kelley PM, Cohn ES, Van Maldergem L, Hilbert P, Roux AF, Mondain M, Hoefsloot LH, Cremers CW, Löppönen T, Löppönen H, Parving A, Gronskov K, Schrijver I, Roberson J, Gualandi F, Martini A, Lina-Granade G, Pallares-Ruiz N, Correia C, Fialho G, Cryns K, Hilgert N, Van de Heyning P, Nishimura CJ, Smith RJ, Van Camp G. GJB2 mutations and degree of hearing loss: a multicenter study. Am J Hum Genet. 2005;77(6):945-57. doi:10.1086/497996. Epub 2005 Oct 19. PMID: 16380907.
Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Kelsell DP, et al. Nature. 1997;387(6628):80-3. doi:10.1038/387080a0. PMID: 9139825.

Pre-test genetic counseling required:

Decline to answer

Post-test genetic counseling required:

Decline to answer

Conditions

Total conditions: 5

Condition/Phenotype	Identifier

Test Targets

Genes

Total genes: 2

Gene	Associated Condition	Germline or Somatic	Allele (Lab-provided)	Variant in NCBI

Methodology

Total methods: 2

Method Category

Test method

Instrument

Deletion/duplication analysis

Multiplex PCR using deletion-specific primers followed by gel electrophoresis

Sequence analysis of the entire coding region

Bi-directional Sanger Sequence Analysis

Applied Biosciences 3500XL DNA sequencer

Clinical Information

Test purpose:

Diagnosis; Mutation Confirmation

Clinical utility:

Establish or confirm diagnosis

View citations (1)

https://morl.lab.uiowa.edu/clinical-diagnostic-services/hearing-loss-otoscope%C2%AE/gjb2-gjb6-dfnb1

Variant Interpretation:

Are family members with defined clinical status recruited to assess significance of VUS without charge?
No.

Will the lab re-contact the ordering physician if variant interpretation changes?
Yes. If new information comes to light about a previously identifed variant that changes the result significantly (ie, the variant was previously reported as damaging and now is considered a benign polymorphism) a revised report will be sent to the ordering physician.

Recommended fields not provided:

Clinical validity, Target population, What is the protocol for interpreting a variation as a VUS?, Is research allowed on the sample after clinical testing is complete?, Sample negative report, Sample positive report

Technical Information

Test Procedure:

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 gel electrophoresis.

View citations (4)

A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. del Castillo I, et al. N Engl J Med. 2002;346(4):243-9. doi:10.1056/NEJMoa012052. PMID: 11807148.
Del Castillo I, Moreno-Pelayo MA, Del Castillo FJ, Brownstein Z, Marlin S, Adina Q, Cockburn DJ, Pandya A, Siemering KR, Chamberlin GP, Ballana E, Wuyts W, Maciel-Guerra AT, Alvarez A, Villamar M, Shohat M, Abeliovich D, Dahl HH, Estivill X, Gasparini P, Hutchin T, Nance WE, Sartorato EL, Smith RJ, Van Camp G, Avraham KB, Petit C, Moreno F. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: a multicenter study. Am J Hum Genet. 2003;73(6):1452-8. doi:10.1086/380205. Epub 2003 Oct 21. PMID: 14571368.
GJB2: the spectrum of deafness-causing allele variants and their phenotype. Azaiez H, et al. Hum Mutat. 2004;24(4):305-11. doi:10.1002/humu.20084. PMID: 15365987.
A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. del Castillo FJ, et al. J Med Genet. 2005;42(7):588-94. doi:10.1136/jmg.2004.028324. PMID: 15994881.

Test Platform:

BigDye Terminator v3.1 and custom oligo primers

Test Confirmation:

Positive results are confirmed on a new DNA preparation, repeating the assays.

Test Comments:

This test is designed to amplify exonic regions of GJB2 and determine the presence or absence of two known deletions, del(GJB6-D13S1830) and del(GJB6-D13S1854). Other copy number variations within GJB6 are not detectable with this assay. Rare sequence variants within primer sites may lead to erroneous results.

Availability:

Tests performed
Interpretation performed in-house
Report generated in-house
Specimen preparation performed both in-house and at an outside lab
Wet lab work performed in-house

Test performance comments
DNA isolation from whole blood can be done by the ordering provider's institutional lab and DNA sent to the MORL for testing.

Analytical Validity:

Greater than 99 percent.

Assay limitations:

Proficiency testing (PT):

Is proficiency testing performed for this test?
Yes

Method used for proficiency testing:
Formal PT program

PT Provider:
European Molecular Genetics Quality Network, EMQN

Description of PT method:
In addition to formal proficiency testing through EMQN, MORL does in-house proficiency testing for this test.

VUS:

Laboratory's policy on reporting novel variations
Data about the variants identified will be provided in a comprehensive report to the ordering healthcare provider.

Recommended fields not provided:

Citations to support assay limitations, Description of internal test validation method, Citations for Analytical validity, Major CAP category, CAP category, CAP test list

Regulatory Approval

FDA Review:

Category: FDA exercises enforcement discretion

Additional Information

Reviews:

Genereviews

PubMed Clinical Queries

Clinical resources:

Molecular resources:

View GJB2 variations in ClinVar

View GJB3 variations in ClinVar

View GJB6 variations in ClinVar

RefSeqGene

Coriell Institute for Medical Research

Practice guidelines:

NICE, 2019

NICE, 2009

Consumer resources:

MalaCards

NCATS Office of Rare Diseases Research (GARD)

MedlinePlus

IMPORTANT NOTE: NIH does not independently verify information submitted to GTR; it relies on submitters to provide information that is accurate and not misleading. NIH makes no endorsements of tests or laboratories listed in GTR. GTR is not a substitute for medical advice. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.