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Microphthalmia and Anophthalmia via the RAX 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
RAX 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3941RAX81479 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.

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


  • Dana Talsness, PhD

Clinical Features and Genetics

Clinical Features

Anophthalmia (A; absence of a globe in the orbit) and microphthalmia (M; reduced size of the globe) are severe and rare developmental defects of the globe with an estimated incidence of 0.2–0.4/10 000 and ~1.5/10 000 live births, respectively (Källén and Tornqvist 2005). Both A/M may be unilateral or bilateral, and over 50% of A/M affected individuals have systemic abnormalities such as hypothalamic–pituitary disorder, mild dysmorphic facial features and short stature, urogenital anomalies, cryptorchidism and/or micropenis in males, developmental delay, seizures, oesophageal atresia or tracheoesophageal fistula and hearing loss (Ragge et al. 2005), but only 25% of these are part of distinct and well-defined syndromes (Bakrania et al. 2007). Unilateral A/M cases often have developmental anomalies of the other eye; including coloboma, lens, and optic nerve (Ragge et al. 2007).


Anophthalmia/Microphthalmia (A/M) may be inherited as an autosomal dominant, autosomal recessive, or X-linked trait. A/M has a complex aetiology with a wide range of causes, including chromosomal abnormalities, as well as environmental factors (Pedace et al. 2009). Chromosomal duplications, deletions and translocations account for 23–30% of A/M cases. Bakrania et al. reported whole SOX2 gene deletions in ~10% of their A/M patients cohort (Bakrania et al. 2007), which emphasizes the necessity of careful chromosomal analysis (particularly the 3q region that comprises the SOX2 gene) (Guichet et al. 2004). SOX2 has been identified as a major causative gene in which heterozygous, loss of function variants account for 15–20% of the A/M cases (Reis et al. 2010; Faivre et al. 2006; Ragge et al. 2005; Williamson and Fitzpatrick 2014). The majority of the causative SOX2 sequence variations are de novo (FitzPatrick 2009). Occasional cases result from parental gonosomal mosaicism (Faivre et al. 2006; Schneider et al. 2008). Heterozygous loss-of-function variants in SOX2 and OTX2 (Wyatt A. et al. 2008) are the most common genetic pathologies associated with severe eye malformations. Bi-allelic loss-of-function variants in STRA6 (Gerth-Kahlert et al. 2013) are confirmed as an emerging cause of nonsyndromal eye malformations.

Pathogenic variants in RAX (retina and anterior neural fold homeobox) cause recessive microophthalmia and anophthalmia (Chassaing et al. 2014). The RAX gene (also known as Rx) is expressed very early in retinal development. Members of the Rx/Rax (retinal homeobox) gene family are shown to be essential for vertebrate eye development. Abnormal expression has been shown to have profound effects on eye development (Pan et al. 2010; Mathers et al. 1997; Bailey et al. 2004). Over ten pathogenic variants (Missense, nonsense, splicing, small and one gross deletion) have been documented causative to date (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Heterozygous loss-of-function variants in SOX2 and OTX2 (Wyatt et al. 2008) are the most common genetic pathologies associated with severe eye malformations. It has been reported that RAX causative variants account for ~1.3 to 3% of all anophthalmia/microphthalmia patients) (Chassaing et al. 2014; Voronina et al. 2004).

Testing Strategy

This test provides full coverage of all coding exons of the RAX 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

Candidates for this test are patients with symptoms consistent recessive Microphthalmia and Anophthalmia. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RAX.


Official Gene Symbol OMIM ID
RAX 601881
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Microphthalmia, Isolated 3 AR 611038

Related Tests

Anterior Segment Dysgenesis via the FOXE3 Gene
Klippel-Feil Syndrome via the GDF6 Gene
Syndromic Microphthalmia via the OTX2 Gene


  • Bailey T.J. et al. 2004. The International Journal of Developmental Biology. 48: 761-70. PubMed ID: 15558469
  • Bakrania P. et al. 2007. The British Journal of Ophthalmology. 91: 1471-6.  PubMed ID: 17522144
  • Chassaing N. et al. 2014. Clinical Genetics. 86: 326-34. PubMed ID: 24033328
  • Faivre L. et al. 2006. American Journal of Medical Genetics. Part A. 140: 636-9. PubMed ID: 16470798
  • FitzPatrick. 2009. SOX2-Related Eye Disorders. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301477
  • Gerth-Kahlert C. et al. 2013. Molecular Genetics & Genomic Medicine. 1: 15-31. PubMed ID: 24498598
  • Guichet A. et al. 2004. Prenatal Diagnosis. 24: 828-32. PubMed ID: 15503273
  • Human Gene Mutation Database (Bio-base).
  • Källén B., Tornqvist K. 2005. European Journal of Epidemiology. 20: 345–350. PubMed ID: 15971507
  • Mathers P.H. et al. 1997. Nature. 387: 603-7. PubMed ID: 9177348
  • Pan Y. et al. 2010. Developmental Biology. 339: 494-506. PubMed ID: 20060393
  • Pedace L. et al. 2009. European Journal of Medical Genetics. 52: 273-6. PubMed ID: 19254784
  • Ragge N.K. et al. 2005. American Journal of Medical Genetics. Part A. 135: 1-7; discussion 8.  PubMed ID: 15812812
  • Ragge N.K. et al. 2007. Eye. 21: 1290-300.  PubMed ID: 17914432
  • Reis L.M. et al. 2010. Molecular Vision. 16: 768-73. PubMed ID: 20454695
  • Schneider A. et al. 2008. American Journal of Medical Genetics Part A 146A: 2794-8. PubMed ID: 18831064
  • Voronina V.A. et al. 2004. Human Molecular Genetics. 13: 315-22. PubMed ID: 14662654
  • Williamson K.A., FitzPatrick D.R. 2014. European Journal of Medical Genetics. 57: 369-80.  PubMed ID: 24859618
  • Wyatt A. et al. 2008. Human Mutation. 29: E278–E283. PubMed ID: 18781617


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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