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Deafness, Autosomal Recessive 16 (DFNB16) via MLPA of STRC

Summary and Pricing

Test Method

Multiplex Ligation-Dependent Probe Amplification Assay
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
12548 STRC 81479 81479 $540 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12548STRC81479 81479(x1) $540 Order Options and Pricing

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

Turnaround Time

20 days on average for standard orders or 14 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

  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Pathogenic variants in STRC are associated with autosomal recessive nonsyndromic hearing loss characterized by moderate to profound non-progressive hearing loss sloping towards high frequencies, with onset being congenital to the first decade (Verpy et al. 2001. PubMed ID: 11687802; Yokota et al. 2019. PubMed ID: 30867468; Vona et al. 2015. PubMed ID: 26011646). 

Hearing loss (HL) or deafness is the most common sensory deficit in humans, affecting an estimated 5% of the world's population (Azaiez et al. 2018. PubMed ID: 30245029). Molecular genetic testing is possible for many types of hearing loss and plays a prominent role in diagnosis, genetic counseling, evaluating hearing loss stability and potential of undiagnosed related clinical features (Shearer et al. 2017. PubMed ID: 20301607).

Genetics

Pathogenic variants in STRC are the second most common cause of autosomal recessive nonsyndromic hearing loss after the GJB2 gene, and have been estimated to account for 80% of causative copy number variants (CNVs) in hearing loss cases. Large STRC deletions are the most common pathogenic variant type with an estimated carrier frequency of 2.6-4.7% across populations, with STRC to STRCP1 gene conversion carrier frequency estimated at 2.6% (Shearer et al. 2014. PubMed ID: 24963352; Yokota et al. 2019. PubMed ID: 30867468).

STRC missense, nonsense and splicing variants have also been reported as pathogenic, although technical care must be taken to ensure the variant in question is located in STRC as opposed to the STRCP1 pseudogene (Schrauwen et al. 2013. PubMed ID: 23208854; Miyagawa et al. 2013. PubMed ID: 23967202; Mandelker et al. 2014. PubMed ID: 25157971).

The vast majority of pathogenic STRC variants appear to be inherited. A knockout mouse model exhibited progressive deafness (Verpy et al. 2008. PubMed ID: 18849963), and the gene is generally considered to be loss of function intolerant.

STRC is located on chromosome 15 at band q15.3, is comprised of 29 exons and encodes the 1,775 amino acid stereocilin protein. STRC is expressed in microvilli called stereocilia projecting from sensory 'hair' cells of the inner ear. STRC links the tips of adjacent stereocilia together, forming hair 'bundles' involved in mechanoreception of sound waves as they pass through the cochlea (Verpy et al. 2001. PubMed ID: 11687802; Vona et al. 2015. PubMed ID: 26011646).

STRC is located within a tandem genomic duplication, with the STRC pseudogene STRCP1 residing in the second copy. The high degree of sequence similarity between STRC and STRCP1, with almost identical coding sequence in exons 1-14, complicates the analysis of this region by short read next-gen sequencing and likely predisposes this locus to structural variation.

Clinical Sensitivity - MLPA

The clinical sensitivity of this test is difficult to estimate given the genetic heterogeneity of hearing loss. The analytical sensitivity of this test is expected to approach 100% for copy number variants that encompass exons 19, 23, 24, and 25. Copy number variants not involving these exons are not expected to be detected due to technical limitations related to the STRCP1 pseudogene.

Testing Strategy

MLPA probes are only able to be placed in STRC exons 19, 23, 24, and 25 due to high sequence paralogy between STRC and the pseudogene STRCP1

Multiplex Ligation-Dependent Probe Amplification (MLPA) enables the detection of deletion and duplications of single and multiple exons within a given gene (Eijk-Van Os and Schouten. 2011. PubMed ID: 20938835). It is a semi-quantitative technique to determine relative copy number using a multiplex PCR-based reaction. Only hybridized and ligated adjacent probe oligonucleotides of approximately 60 nucleotides in length are amplified using PCR and thus are specific for the sequence of interest. A stuffer sequence attached to the probe ensures a particular length for deciphering the probe target. Therefore, MLPA enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. For additional information please see www.mlpa.com.

Indications for Test

This test may be considered for patients with nonsyndromic hearing loss. Given the high frequency of pathogenic STRC large deletions, testing for copy number variation via MLPA should be considered prior to or in conjunction with Sanger sequencing. This test may also be considered for patients in which a single STRC sequence variant has already been identified for this autosomal recessive disorder.

Gene

Official Gene Symbol OMIM ID
STRC 606440
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Deafness, Autosomal Recessive 16 AR 603720

Citations

  • Azaiez et al. 2018. PubMed ID: 30245029
  • Eijk-Van Os and Schouten. 2011. PubMed ID: 20938835
  • Mandelker et al. 2014. PubMed ID: 25157971
  • Miyagawa et al. 2013. PubMed ID: 23967202
  • Schrauwen et al. 2013. PubMed ID: 23208854
  • Shearer et al. 2014. PubMed ID: 24963352
  • Verpy et al. 2001. PubMed ID: 11687802
  • Verpy et al. 2008. PubMed ID: 18849963
  • Vona et al. 2015. PubMed ID: 26011646
  • Yokota et al. 2019. PubMed ID: 30867468

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.
Total Price: $
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