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Dyskeratosis Congenita (DC) and Hoyeraal-Hreidarsson Syndrome via the DKC1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7627 DKC1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7627DKC181479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days 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. 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).

Variants in the DKC1 gene also cause Hoyeraal-Hreidarsson syndrome (HHS), a severe type of DC which is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation. Children with HHS often die in the first decade of life due to bone marrow failure. Both DC and HHS patients have markedly shorter telomeres than age-matched healthy individuals (Heiss et al. 1998. PubMed ID: 9590285; Knight et al. 1999. PubMed ID: 10583221; Knight et al. 1999. PubMed ID: 10364516; Savage et al. 2016. PubMed ID: 20301779).

Genetics

Dyskeratosis congenita is caused primarily from 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 as well as TERT (Savage et al. 2016. PubMed ID: 20301779).

DKC1-related DC and HHS are inherited in an X-linked manner. Development of clinical features in a female carrier who is heterozygous for a DKC1 pathogenic variant is extremely rare (Savage et al. 2016. PubMed ID: 20301779). The DKC1 gene encodes Dyskerin, which is a component of telomerase complex and belongs to the small nucleolar ribonucleoproteins family needed for ribosome biogenesis and maintenance of proper telomere structure. The great majority of causative variants are missense or small in-frame deletions (2/71) (Savage et al. 2016. PubMed ID: 20301779; Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

Approximately 70% of individuals with dyskeratosis congenita (DC) have pathogenic variants in at least 1 of the 11 known DC genes. DKC1 accounts for ~20-25% of pathogenic variants reported in DC patients (Savage et al. 2016. PubMed ID: 20301779).

Testing Strategy

This test provides full coverage of all coding exons of the DKC1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with X-linked Dyskeratosis Congenita, Hoyeraal-Hreidarsson syndrome and the family members of patients who have known DKC1 variants.

Gene

Official Gene Symbol OMIM ID
DKC1 300126
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Dyskeratosis Congenita X-Linked XL 305000

Related Test

Name
Interstitial Lung Disease Panel

Citations

  • Heiss et al. 1998. PubMed ID: 9590285
  • Human Gene Mutation Database (Bio-base).
  • Kirwan et al. 2008. PubMed ID: 18005359
  • Knight et al. 1999. PubMed ID: 10583221
  • Knight et al. 1999. PubMed ID: 10364516
  • Savage et al. 2016. PubMed ID: 20301779
  • Trahan et al. 2010. PubMed ID: 20008900
  • 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

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.
Total Price: $
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