SOX2-Related Ocular Disorders via the SOX2 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1543 SOX2$610.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

A mutation analysis in a cohort of 120 patients with congenital eye abnormalities, mainly A/M and coloboma, identified pathogenic variations in the coding region of the SOX2 gene in 6 patients and whole gene deletions in 5 patients (Bakrania et al. 2007). Another mutation screening in a cohort of 51 unrelated individuals affected with bilateral (38) or unilateral (13) A/M revealed SOX2 mutations in ten patients (19.6%). Seven of them had novel alterations, while the remaining three individuals had previously reported a recurrent 20-nucleotide deletion designated c.70_89del20. This deletion accounts for 30% of SOX2 mutations in their cohort (Schneider et al. 2009) and ~21% of all SOX2 cases that have been reported to date (Reis et al. 2010).

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 SOX2$690.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price













Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Features

Congenital ocular malformations: 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 tracheooesophageal 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).


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). Of monogenic causes, only SOX2 [Sex determining region Y (SRY)-box 2] has been identified as a major causative gene in which heterozygous, loss of function mutations account for 10–20% of the A/M cases (Reis et al. 2010; Faivre et al. 2006; Ragge et al. 2005; Williamson 2006). Other A/M associated genes include PAX6, SIX6, HESX1, BCOR, SHH, RAX, CHD7, IKBKG, NDP, POMT1, GDF6, VSX2 and SIX3 (Bardakjian et al. 2006; Slavotinek 2011). SOX2-related ocular disorder is inherited in an autosomal dominant manner, and 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).

Sox2 is a member of the Sox family of proteins, which encodes an SRY-like HMG (High Mobility Group) box transcription factor. The HMG domain among Sox proteins is highly conserved and is critical for correct binding to interacting proteins (Williamson 2006). Sox2 plays a key regulatory role in lens development and is reported to interact with Oct-1 and Pax6 to control lens and nasal placode development (Kamachi et al. 2001; Donner et al. 2007).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of  the single coding exon of the SOX2 gene plus ~10 bp of flanking non-coding DNA on either side are sequenced. We will also sequence any single portion (Test #100) of this exon in family members of patients with a known mutation or to confirm research results.

Indications for Test

Candidates for this test are patients with symptoms consistent with SOX2-related eye disorders and family members of patients who have known mutations.


Official Gene Symbol OMIM ID
SOX2 184429
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Microphthalmia Syndromic 3 206900

Related Test

Anophthalmia / Microphthalmia Sequencing Panel


Genetic Counselors
  • Bakrania P. et al. 2007. The British Journal of Ophthalmology. 91: 1471-6.  PubMed ID: 17522144
  • Bardakjian et al. 2013. Microphthalmia/Anophthalmia/Coloboma Spectrum. 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: 20301552
  • Donner AL, Episkopou V, Maas RL. 2007. Sox2 and Pou2f1 interact to control lens and olfactory placode development. Developmental Biology 303: 784–799. PubMed ID: 17140559
  • 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
  • Guichet A. et al. 2004. Prenatal Diagnosis. 24: 828-32. PubMed ID: 15503273
  • Källén B, Tornqvist K. 2005. European Journal of Epidemiology. 20: 345–350. PubMed ID: 15971507
  • Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H. 2001. Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Genes & development 15: 1272–1286. PubMed ID: 11358870
  • Pedace et al. 2009. European Journal of Medical Genetics. 52: 273–276. 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 (london, England). 21: 1290-300.  PubMed ID: 17914432
  • Reis L.M. et al. 2010. Molecular Vision 16: 768-73. PubMed ID: 20454695
  • Schneider A, Bardakjian T, Reis LM, Tyler RC, Semina EV. 2009. Novel SOX2 mutations and genotype-phenotype correlation in anophthalmia and microphthalmia. American Journal of Medical Genetics Part A 149A: 2706–2715. PubMed ID: 19921648
  • Schneider A. et al. 2008. American Journal of Medical Genetics Part A 146A: 2794-8. PubMed ID: 18831064
  • Slavotinek AM. 2011. Eye development genes and known syndromes. Molecular Genetics and Metabolism 104: 448–456. PubMed ID: 22005280
  • Williamson KA. 2006. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Human Molecular Genetics 15: 1413–1422. PubMed ID: 16543359
Order Kits

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH 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. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×