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Deafness, X-Linked 4 (DFNX4) via the SMPX Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
SMPX 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4027SMPX81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • Ben Dorshorst, PhD

Clinical Features and Genetics

Clinical Features

Nonsyndromic hearing loss is characterized by difficulty or inability to hear that is not associated with any visible defects involving the external ear, other organs, or any other medical condition. Nonsyndromic hearing loss may be associated with abnormalities involving the middle ear and/or the inner ear (Ciuman 2013; Dodson et al. 2011; Hilgert et al. 2009). At least 70% of cases involving hearing loss are nonsyndromic (Van Camp et al. 1997).

Nonsyndromic hearing loss and deafness due to pathogenic variants in the SMPX gene is associated with postlingual, bilateral, moderate to profound, progressive sensorineural hearing impairment beginning in the high frequencies. No vestibular abnormalities are present (Huebner et al. 2011; Schraders et al. 2011; Weegerink et al. 2011).


DFNX4 is a sex-linked dominant hearing disorder that is caused by pathogenic sequence variants in the small muscle protein, X-linked (SMPX) gene, which is located on chromosome Xp22.12 .Age of onset is in the first decade for males and first to fourth decade for females. In female carriers penetrance is incomplete with 70% of individuals showing moderate to severe hearing loss at high frequencies by the fourth decade (Weegerink et al. 2011).

The SMPX gene spans 56 kb and consists of 3 coding exons that produce a 88 amino acid protein. The SMPX gene is expressed in fetal and adult skeletal muscle and heart, fetal inner ear and adult retina. The exact role of the SMPX protein in inner ear function remains unknown, although it is thought to be involved in the development and/or maintenance of the sensory hair cells through association with the cytoskeleton (Huebner et al. 2011; Schraders et al. 2011).

Missense, nonsense, splicing and small deletion variants in SMPX have been reported as pathogenic for hearing loss, with about 10 variants reported to date in different families showing X-linked inheritance (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

In a study of 1,119 patients with hearing loss in which 440 patients received a genetic diagnosis, only two pathogenic variants in the SMPX gene were detected (Sloan-Heggen et al. 2016). Missense, nonsense, splicing and small deletion variants in SMPX have been reported as pathogenic for hearing loss, with about 10 variants reported to date in different families showing dominant X-linked inheritance (Human Gene Mutation Database). Analytical sensitivity should be high because all reported variants are detectable by sequencing.

The clinical sensitivity of CNV detection is unknown. No large deletion or duplication variants associated with SMPX have been reported as pathogenic for hearing loss.

Testing Strategy

This test provides full coverage of all coding exons of the SMPX gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Nonsyndromic hearing loss and deafness due to variants in the SMPX gene is suspected in individuals with the following: postlingual, bilateral, moderate to profound, progressive sensorineural hearing impairment beginning in the high frequencies; no related systemic findings identified by medical history and physical examination; and/or a family history of nonsyndromic hearing loss consistent with dominant X-linked inheritance.


Official Gene Symbol OMIM ID
SMPX 300226
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Deafness, X-Linked 4 XL 300066


  • Ciuman R.R. 2013. Medical Science Monitor. 19: 1195-210. PubMed ID: 24362017
  • Dodson K.M. et al. 2011. American Journal of Medical Genetics. Part A. 155A: 993-1000. PubMed ID: 21465647
  • Hilgert N. et al. 2009. Mutation Research. 681: 189-96. PubMed ID: 18804553
  • Huebner A.K. et al. 2011. American Journal of Human Genetics. 88: 621-7. PubMed ID: 21549336
  • Human Gene Mutation Database (Bio-base).
  • Schraders M. et al. 2011. American Journal of Human Genetics. 88: 628-34. PubMed ID: 21549342
  • Sloan-Heggen C.M. et al. 2016. Human Genetics. 135: 441-50. PubMed ID: 26969326
  • Van Camp G. et al. 1997. American Journal of Human Genetics. 60: 758-64. PubMed ID: 9106521
  • Weegerink N.J. et al. 2011. Hearing Research. 282: 167-77. PubMed ID: 21893181


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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