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Dyskeratosis Congenita (DC) via the PARN 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
10649 PARN 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10649PARN81479 81479,81479 $990 Order Options and Pricing

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).

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

Clinical Features

Dyskeratosis congenita (DC) is a disease characterized by multiple anomalies including abnormal skin pigmentation, nail dystrophy, mucosal leukoplakia, bone marrow failure and an increase in cancer predisposition (Walne et al. 2007. PubMed ID: 17507419; Kirwan et al. 2008. PubMed ID: 18005359). Individuals affected with DC can exhibit other features including liver cirrhosis, osteoporosis, pulmonary fibrosis and learning difficulties (Dvorak et al. 2015. PubMed ID: 25455995). Approximately 80-90% of individuals affected with DC experience bone marrow failure by age 30 (Kirwan et al. 2008. PubMed ID: 18005359). Age of onset and progression of DC may vary. Those who have minimal physical findings with normal bone marrow function are at the mild end of the spectrum, while those at the severe end of the spectrum have these features along with bone marrow failure (Savage et al. 2016. PubMed ID: 20301779).

Genetics

Dyskeratosis congenita is caused primarily by defects in telomere maintenance (Walne et al. 2007. PubMed ID: 17507419; Trahan et al. 2010. PubMed ID: 20008900). DC is characterized by three genetic subtypes: X-linked recessive, caused by variants in the DKC1 gene, autosomal dominant DC caused by heterozygous variants in TERC, TINF2 or TERT genes, and autosomal recessive DC which involves several genes including ACD, CTC1, DKC1, NHP2, NOP10, PARN, RTEL1, WRAP53 and TERT (Savage et al. 20016. PubMed ID: 20301779).

PARN is a poly (A)-specific ribonuclease that acts by shortening the length of mRNA poly (A) tail through the process of deadenylation. PARN has been shown to be required for the 3’-end maturation of TERC, the RNA component of telomerase (Moon et al. 2015. PubMed ID: 26482878; Savage et al. 2016. PubMed ID: 20301779). Individuals with biallelic pathogenic variants in PARN exhibit a reduction in RNA levels for several key genes associated with telomere biology including TERC, DKC1, RTEL1 and TERT (Tummala et al. 2015. PubMed ID: 25893599).

Pathogenic variants in PARN have also been identified individuals with Hoyeraal-Hreidarsson syndrome, as well as autosomal dominant pulmonary fibrosis (Burris et al. 2016. PubMed ID: 26810774; Savage et al. 2016. PubMed ID: 20301779). To date, there have been ~30 reported causative PARN variants which include missense, nonsense, splicing, small frameshift and gross deletions, and small frameshift insertions, 8 of which are directly related to DC (Human Genome Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Approximately 70% of individuals with dyskeratosis congenita (DC) have pathogenic variants in at least 1 of the 11 known DC genes. PARN accounts for <1% of pathogenic variants reported in DC patients, as these variants have only been reported in a few patients (Savage et al. 20016. PubMed ID: 20301779; Moon et al. 2015. PubMed ID: 26482878; Tummala et al. 2015. PubMed ID: 25893599; Burris et al. 2016. PubMed ID: 26810774).

Testing Strategy

This test provides full coverage of all coding exons of the PARN 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 autosomal recessive Dyskeratosis Congenita or Hoyeraal-Hreidarsson syndrome and the family members of patients who have known PARN variants. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PARN.

Gene

Official Gene Symbol OMIM ID
PARN 604212
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Interstitial Lung Disease Panel

Citations

  • Burris et al. 2016. PubMed ID: 26810774
  • Dvorak et al. 2015. PubMed ID: 25455995
  • Human Gene Mutation Database (Bio-base).
  • Kirwan et al. 2008. PubMed ID: 18005359
  • Moon et al. 2015. PubMed ID: 26482878
  • Savage et al. 2016. PubMed ID: 20301779
  • Trahan et al. 2010. PubMed ID: 20008900
  • Tummala et al. 2015. PubMed ID: 25893599
  • Walne et al. 2007. PubMed ID: 17507419

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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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