Pendred Syndrome and Nonsyndromic Hearing Loss Associated with Enlarged Vestibular Aqueduct via the SLC26A4 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
4861 SLC26A4 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4861SLC26A481406 81406(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.

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Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Pendred syndrome is a congenital or prelingual sensorineural hearing impairment disorder that generally causes severe to profound hearing loss and other findings. Clinical features, in addition to hearing loss, can include an enlarged vestibular aqueduct (EVA), temporal bone abnormalities, and development of euthyroid goiter in late childhood to early adulthood (Smith. 2017. PubMed ID: 20301640). Individuals with Pendred syndrome who have EVA can also have cochlear hypoplasia, which when both are present are termed Mondini malformation/dysplasia. Deafness, autosomal recessive 4 (DFNB4) is characterized by nonsyndromic sensorineural hearing impairment, vestibular dysfunction, and enlarged vestibular aqueduct (EVA). Thyroid defects are not seen in DFNB4. Both Pendred syndrome and DFNB4 are caused by a partial iodide organification defect. This abnormality can be detected using a perchlorate test, which determines whether iodide is organified normally into thyroglobulin (Bizhanova and Kopp. 2010. PubMed ID: 20298745).

Genetics

Pendred syndrome and DFNB4 are autosomal recessive disorders that show variable expressivity, even within the same family. They are caused by variants in the solute carrier family 26 member 4 (SLC26A4), (forkhead box I1) FOXI1, and (potassium voltage-gated channel subfamily J member 10) KCNJ10 genes.

Variants in SLC26A4 are the third most common cause of autosomal recessive hearing loss overall and explain 50% of Pendred syndrome and DFNB4 cases (Smith. 2017. PubMed ID: 20301640; Hilgert et al. 2009. PubMed ID: 18804553). SLC26A4, which encodes the pendrin protein, is a chloride, iodide, bicarbonate, and formate transporter. Pendrin is expressed in the thyroid, the inner ear, and the kidney (Bizhanova and Kopp. 2010. PubMed ID: 20298745). Individuals with Pendred syndrome or DFNB4 are often compound heterozygous for variants in SLC26A4, but only one heterozygous causative variant is found in approximately 10% and 25% of Asian and Caucasian families, respectively (Smith. 2017. PubMed ID: 20301640). More than 400 causative variants have been reported in SLC26A4 consisting of missense, nonsense, splicing, regulatory, small frameshift insertions/deletions and large deletions (Human Gene Mutation Database).

Variants in the FOXI1 and KCNJ10 genes have also been reported in patients with nonsyndromic hearing loss and EVA and a single SLC26A4 variant (Yang et al. 2007. PubMed ID: 17503324; Yang et al. 2009. PubMed ID: 19426954).

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in SLC26A4 are the third most common cause of autosomal recessive hearing loss overall and explain 50% of Pendred syndrome and DFNB4 cases (Smith. 2017. PubMed ID: 20301640; Hilgert et al. 2009. PubMed ID: 18804553).

A study involving 107 patients with sensorineural hearing loss with inner ear malformations and a single heterozygous causative variant in SLC26A4 identified a large deletion in only a single patient, indicating the clinical sensitivity for deletion and duplication analysis is low (Pique et al. 2014. PubMed ID: 24860705). Only 6 large deletions have been reported in SLC26A4 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the SLC26A4 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

In addition to the regions described above, this test includes coverage of the following variants that reside in untranslated or deep intronic regions: SLC26A4 non-coding exon 1 (including c.-103T>C, c.-60A>G and c.-4+1G>C).

Indications for Test

Individuals with sensorineural hearing loss and enlarged vestibular aqueduct (EVA). Individuals may also display temporal bone abnormalities, euthyroid goiter, cochlear hypoplasia, Mondini malformation/dysplasia or positive perchlorate discharge test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SLC26A4.

Gene

Official Gene Symbol OMIM ID
SLC26A4 605646
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Enlarged Vestibular Aqueduct Syndrome AR 600791
Pendred Syndrome AR 274600

Related Tests

Name
Congenital Hypothyroidism and Thyroid Hormone Resistance Panel
Pendred Syndrome and Nonsyndromic Hearing Loss Associated with Enlarged Vestibular Aqueduct Panel
Pendred Syndrome and Nonsyndromic Hearing Loss Associated with Enlarged Vestibular Aqueduct via the FOXI1 Gene
Pendred Syndrome and Nonsyndromic Hearing Loss Associated with Enlarged Vestibular Aqueduct via the KCNJ10 Gene

Citations

  • Bizhanova and Kopp. 2010. PubMed ID: 20298745
  • Hilgert et al. 2009. PubMed ID: 18804553
  • Human Gene Mutation Database (Bio-base).
  • Pique et al. 2014. PubMed ID: 24860705
  • Smith. 2017. PubMed ID: 20301640
  • Yang et al. 2007. PubMed ID: 17503324
  • Yang et al. 2009. PubMed ID: 19426954

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)


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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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