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Treacher Collins Syndrome via the POLR1D Gene

Order Options and Pricing
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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
POLR1D 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9223POLR1D81479 81479,81479 $990 Order Options and Pricing

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Stela Berisha, PhD, FACMG

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.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Indications for Test

Candidates for this test are patients with symptoms consistent with Treacher Collins Syndrome, and the family members of patients who have known POLR1D mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in POLR1D.

Clinical Features

Treacher Collins syndrome (TCS, also called mandibulofacial dysostosis or Franceschetti-Kelin syndrome) is a craniofacial malformation disorder characterized by downward slanting palpebral fissures, lower eyelid colobomas, microtia, and malar and mandibular hypoplasia. Other features include cleft palate, malformation of external ear canals, and bilateral conductive hearing loss (Dixon 1996; Chang et al. 2012). Clinical presentations of TCS are highly variable. TCS shares some facial dysmorphic features with other syndromes such as Pierre-Robin, Miller syndrome, Nager syndrome, and Goldenhar syndrome. It can be further divided into three subtypes: TCS type 1 is inherited in an autosomal dominant manner and is caused by mutations in TCOF1. TCS type 2 is inherited in both autosomal dominant and autosomal recessive manners and is caused by mutations in POLR1D. TCS type 3 is inherited in an autosomal recessive form and is caused by mutations in POLR1C (Dixon et al. 1996; Dauwerse et al. 2011; Katsanis and Jabs 2012, Schaefer et al. 2014).

Genetics

TCS Type 2 is inherited in both autosomal dominant and recessive manners and is caused by mutations in the POLR1D gene. Polymerase (RNA) I polypeptide D, 16kDa coded by POLR1D, is a subunit of RNA polymerase I and III. Both RNA polymerase I and III are involved in ribosomal RNA transcription. RNA polymerase III predominantly involves synthesis of 5S ribosomal RNA and transfer RNA. To date, 18 unique causative mutations have been identified in 20 unrelated index TCS patients. These mutations are:  missense (7/18), nonsense (4/18), splicing (1/18), small deletion/insertions (5/18) and large deletion (1/18). Almost all the mutations are located in in exon 2, except for the one splicing mutation and the one large deletion (Human Gene Mutation Database). The nonsense mutation c.259C>T (p.Arg87*) was found in three unrelated TCS families. Non-penetrance was seen in one of the four families with POLR1D mutations. Note that exon numbering differ from  Dauwerse's publication (Dauwerse et al 2011) due to different reference sequences.

Clinical Sensitivity - Sequencing with CNV PGxome

POLR1D mutations were identified in 20 out of 242 (8%) unrelated TCS patients who were negative for TCOF1 mutations. To date, only one large deletion has been reported (Dauwerse et al. 2011).

Testing Strategy

This test provides full coverage of all coding exons of the POLR1D 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 with Treacher Collins Syndrome, and the family members of patients who have known POLR1D mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in POLR1D.

Gene

Official Gene Symbol OMIM ID
POLR1D 613715
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Treacher Collins Syndrome 2 613717

Citations

  • Chang C, Steinbacher D. 2012. Treacher Collins Syndrome. Seminars in Plastic Surgery 26: 083–090. PubMed ID: 23633935
  • Dauwerse JG, Dixon J, Seland S, Ruivenkamp CAL, Haeringen A van, Hoefsloot LH, Peters DJM, Boers AC, Daumer-Haas C, Maiwald R, Zweier C, Kerr B, Cobo AM, Toral JF, Hoogeboom AJ, Lohmann DR, Hehr U, Dixon MJ, Breuning MH, Wieczorek D. 2010. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature Genetics 43: 20–22. PubMed ID: 21131976
  • Dauwerse JG, Dixon J, Seland S, Ruivenkamp CAL, Haeringen A van, Hoefsloot LH, Peters DJM, Boers AC, Daumer-Haas C, Maiwald R, Zweier C, Kerr B, Cobo AM, Toral JF, Hoogeboom AJ, Lohmann DR, Hehr U, Dixon MJ, Breuning MH, Wieczorek D. 2010. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature Genetics 43: 20–22. PubMed ID: 21131976
  • Dauwerse JG, Dixon J, Seland S, Ruivenkamp CAL, Haeringen A van, Hoefsloot LH, Peters DJM, Boers AC, Daumer-Haas C, Maiwald R, Zweier C, Kerr B, Cobo AM, Toral JF, Hoogeboom AJ, Lohmann DR, Hehr U, Dixon MJ, Breuning MH, Wieczorek D. 2010. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature Genetics 43: 20–22. PubMed ID: 21131976
  • Dixon MJ. 1996. Treacher Collins syndrome. Human molecular genetics 5: 1391–1393. PubMed ID: 8875242
  • Human Gene Mutation Database (Bio-base).
  • Katsanis SH, Jabs EW. 2012. Treacher Collins Syndrome. 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: 20301704
  • Schaefer E, Collet C, Genevieve D, Vincent M, Lohmann DR, Sanchez E, Bolender C, Eliot M-M, Nürnberg G, Passos-Bueno M-R, Wieczorek D, Maldergem L van, Doray B. 2014. Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genetics in Medicine. PubMed ID: 24603435

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

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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