Congenital Fibrosis of Extraocular Muscles (Ocular Motility Disorder) Type 3A via the TUBB3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
8971 TUBB3$890 81479,81479 Add to Order

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.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Congenital fibrosis of extraocular muscles (CFEOM) is an eye movement disorder characterized mainly by non-progressive, restrictive ophthalmoplegia of the extraocular muscles (EOM) and congenital blepharoptosis (Heidary et al. 2008). Congenital fibrosis of extraocular muscles (CFEOM) is a heterogeneous disorder. Depending on the gene, the disease has been categorized into different types. CFEOM1 (due to KIF21A variants), CFEOM2 (due to ARIX variants), CFEOM3A (due to TUBB3 variants), CFEOM3B (due to KIF21A variants), and CFEOM4, CFEOM5 (no genes identified yet) (Oystreck et al. 2011; Traboulsi 2004).

CFEOM3A affected patients may have additional neurological signs or symptoms such as intellectual disability, social disability, facial weakness, and progressive sensorimotor axonal polyneuropathy (Andrews et al. 1993).

Genetics

CFEOM3A is an autosomal dominant disorder, which is due to heterozygous variants in TUBB3. TUBB3 encodes neuron-specific beta-tubulin subunit, which is required for axon guidance and maintenance in mammals (Poirier et al. 2010; Tischfield et al. 2010). In vitro studies using yeast have shown that the TUBB3 causative variants can impair tubulin heterodimer formation and disrupt the interaction of microtubules with kinesin motors. This in turn leads to innervation abnormalities in the EOM during the development of oculomotor and/or trochlear nerves (Tischfield et al. 2010). CFEOM3A is variable, asymmetrical, and variably penetrant (~90%) (Doherty et al 1999). A mutation screen involving 29 unrelated families revealed that 13 had eight TUBB3 pathogenic variants and all occurred de novo (Tischfield et al. 2010). Severe phenotype has been reported in patients with de novo mutations in TUBB3 (Poirier et al. 2010). So far only missense variants have shown to be causative for TUBB3-associated disorders (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TUBB3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

Predicting clinical sensitivity for the TUBB3 gene is challenging due to genetic heterogeneity of Congenital fibrosis of extraocular muscles. However, analytical sensitivity should be high as all the reported variants are detectable by sequencing. TUBB3 mutation screening in 6 unrelated individuals with sporadic CFEOM3A identified de novo pathogenic variants in all the affected patients (Tischfield et al. 2010).

Indications for Test

Patients with congenital abnormalities of eye movements are candidates ((Oystreck et al. 2011; http://novel.utah.edu/diseases/rare-registry/view/Unusual_Congenital_Ocular_Motility_Disorders).

Gene

Official Gene Symbol OMIM ID
TUBB3 602661
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Congenital Fibrosis of Extraocular Muscles (Ocular Motility Disorder) or Strabismus Syndromes Panel

Citations

  • Andrews CV et al. 2011. Congenital Fibrosis of the Extraocular Muscles. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301522
  • Doherty EJ. et al. 1999. Investigative ophthalmology & visual science. 40: 1687-94. PubMed ID: 10393037
  • Heidary et al. 2008. Semin Ophthalmol 23: 3–8. PubMed ID: 18214786
  • Human Gene Mutation Database (Bio-base).
  • NANOS Collection of Unusual Congenital Ocular Motility Disorders and Strabismus
  • Oystreck DT. et al. 2011. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 31: 69-77.  PubMed ID: 21317732
  • Poirier K. et al. 2010. Human molecular genetics. 19: 4462-73.  PubMed ID: 20829227
  • Tischfield MA. et al. 2010. Cell. 140: 74-87.  PubMed ID: 20074521
  • Traboulsi EI. 2004. Transactions of the American Ophthalmological Society. 102: 373-89. PubMed ID: 15747768

Ordering/Specimens

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.

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.

Specimen Types

loading Loading... ×

Copy Text to Clipboard
×