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Dyskeratosis Congenita (DC) and Related Telomere Biology Disorders Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
ACD 81479,81479
CTC1 81479,81479
DKC1 81479,81479
NAF1 81479,81479
NHP2 81479,81479
NOP10 81479,81479
PARN 81479,81479
POT1 81479,81479
RPA1 81479,81479
RTEL1 81479,81479
STN1 81479,81479
TERC 81479,81479
TERT 81479,81479
TINF2 81479,81479
USB1 81479,81479
WRAP53 81479,81479
ZCCHC8 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
3005Genes x (17)81479 81479(x34) $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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 rare inherited disorder associated with impaired telomere maintenance resulting in short telomeres. The phenotypic spectrum is broad and includes individuals affected with classic DC involving multiorgan symptoms, as well as individuals with very short telomeres and isolated clinical findings. Classic DC is primarily characterized by a triad of cardinal phenotypic features including dysplastic fingernails and toenails, reticular skin pigmentation of the neck and upper chest, and oral leukoplakia (Vulliamy et al. 2006. PubMed ID: 16332973; Savage et al. 2023. PubMed ID: 20301779). In addition, patients with DC have increased risk for bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), solid tumors, and pulmonary fibrosis (Walne et al. 2007. PubMed ID: 17507419; Kirwan et al. 2008. PubMed ID: 18005359). Other minor findings in patients with DC include excessive watering of the eyes, inflammation of the eyelids, abnormal eyelash growth, prematurely grey hair, alopecia, dental abnormalities, short stature, microcephaly, developmental delay, hypogonadism, liver cirrhosis, osteoporosis, gastrointestinal telangiectasias, and pulmonary arteriovenous malformations (Savage et al. 2023. PubMed ID: 20301779; Savage. 2022. PubMed ID: 36485133). A diagnosis of DC in an individual with characteristic clinical findings can be established by determining the lymphocyte telomere length and/or identifying pathogenic variants in genes associated with dyskeratosis congenita/telomere biology disorder(s) (Savage et al. 2023. PubMed ID: 20301779).

Although DC is a rare condition, the exact prevalence is unknown. Age of onset and progression of DC varies considerably among individuals, even among individuals within the same family. Three more severe forms of DC/telomere biology disorders (TBD) have been identified to date: Hoyeraal-Hreidarsson syndrome (HHS), Revesz syndrome (RS), and Coats plus syndrome (Savage et al. 2023. PubMed ID: 20301779). Individuals with HHS present with classical features of DC/TBD in early in childhood. Additional clinical findings include cerebellar hypoplasia, developmental delay, immunodeficiency, and bone marrow failure (Hoyeraal et al. 1970. PubMed ID: 5442429; Hreidarsson et al. 1988. PubMed ID: 3201986). Individuals with RS also present in early childhood with classical features of DC/TBD and bilateral exudative retinopathy. In addition, these individuals may have intracranial calcifications and bone marrow failure (Revesz et al. 1992. PubMed ID: 1404302; Savage et al. 2023. PubMed ID: 20301779). Individuals with cerebroretinal microangiopathy with calcifications and cysts, also known as "Coats plus" syndrome, may present with dystrophic nails, sparse or graying hair, bilateral exudative retinopathy, retinal telangiectasias, intracranial calcifications, osteopenia with tendency to fracture with poor bone healing, and gastrointestinal vascular ectasias (Linnankivi et al. 2006. PubMed ID: 16943371, Briggs et al. 2008. PubMed ID: 18076099; Anderson et al. 2012. PubMed ID: 22267198, Polvi et al. 2012. PubMed ID: 22387016). The clinical spectrum of DC is broad, and the manifesting symptoms appear at different ages. Therefore the medical management is specific to each patient and may involve comprehensive care that needs coordination among different specialties. Genetic testing may assist in establishing a diagnosis and predicting the course of disease.

Genetics

The mode of inheritance of dyskeratosis congenita and the related telomere biology disorders (DC/TBD) depends on the gene involved. DC is characterized by three genetic modes of inheritance: X-linked recessive (DKC1), autosomal dominant (NAF1, RPA1, TERC, TINF2, and ZCCHC8), autosomal dominant or autosomal recessive (ACD, PARN, RTEL1 and TERT), and autosomal recessive (CTC1, NHP2, NOP10, POT1, STN1, USB1 and WRAP53). Female carriers of X-linked DKC1 pathogenic variants have been shown to manifest some DC symptoms possibly related to their skewed X-inactivation status (Alder et al. 2013. PubMed ID: 23946118). Individuals with autosomal dominant DC may inherit the pathogenic variant from an affected parent, while others may have the disorder because of a de novo variant. Most of the TINF2 variants have been documented de novo, while the proportion of affected individuals by de novo variants in other genes is currently unknown (Savage et al. 2023. PubMed ID: 20301779). In rare cases, the proband may inherit a pathogenic variant from a parent with germline mosaicism. Individuals with heterozygous pathogenic variants in genes associated with both AD and AR modes of inheritance may be at elevated risk for DC/TBD-related complications (Savage et al. 2023. PubMed ID: 20301779). 

In addition, tissue-restricted mosaicism has been reported in a limited number of individuals with DC/TBD (Jongmans et al. 2012. PubMed ID: 22341970; Sharma et al. 2022. PubMed ID: 34767620). Hence, genetic testing of an alternative tissue, such as skin biopsy, may be considered for individuals who meet the diagnostic criteria for DC/TBD, but do not have a pathogenic variant identified on molecular genetic testing. 

Pathogenic variants in USB1 have also been documented in individuals with autosomal recessive poikiloderma with neutropenia (PN). These individuals have many overlapping clinical features with DC (dystrophic nails, abnormal skin pigmentation and increased risk for myelodysplastic syndrome), but without the characteristic short telomeres (Walne et al. 2010. PubMed ID: 20817924; Walne et al. 2016. PubMed ID: 27612988; Colombo et al. 2018. PubMed ID: 29770900). Due to the significant phenotypic overlap, we have included this autosomal recessive gene in this panel.

Clinical Sensitivity - Sequencing with CNV PGxome

Approximately 80% of individuals with dyskeratosis congenita (DC) have pathogenic variants in at least one of the 16 known DC genes (Savage et al. 2023. PubMed ID: 20301779). Pathogenic variants in DKC1, TINF2, TERC, RTEL1, TERT, and CTC1 genes account for 20%-25%, 12%-20%, 5%-10%, 2%-8%, 1%-7%, and 1%-3% of pathogenic variants in DC cases, respectively. Approximately 20% of patients with clinical findings of DC do not have a molecular finding (Savage et al. 2023. PubMed ID: 20301779).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides approximately 99.9% coverage of all coding exons of the genes 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 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 clinical features consistent with a diagnosis of dyskeratosis congenital (DC). Targeted testing for causative variants in family members of affected individuals is also available. Genetic testing for DC should be considered in individuals with a history of clinical features of DC such as dysplastic fingernails and toenails, reticular skin pigmentation of the neck and upper chest, and oral leukoplakia, a family history of DC, progressive BMF, early onset myelodysplastic syndrome or acute myeloid leukemia, solid tumors of the head and neck, idiopathic or familial pulmonary fibrosis, and short telomere length as determined by flow-FISH.

Genes

Official Gene Symbol OMIM ID
ACD 609377
CTC1 613129
DKC1 300126
NAF1 617868
NHP2 606470
NOP10 606471
PARN 604212
POT1 606478
RPA1 179835
RTEL1 608833
STN1 613128
TERC 602322
TERT 187270
TINF2 604319
USB1 613276
WRAP53 612661
ZCCHC8 616381
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Aml - Acute Myeloid Leukemia 601626
Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 1 XL 301108
Cataracts, hearing impairment, nephrotic syndrome, and enterocolitis 2 AR 620425
Cerebroretinal Microangiopathy with Calcifications and Cysts AR 612199
Cerebroretinal microangiopathy with calcifications and cysts 2 AR 617341
Cerebroretinal microangiopathy with calcifications and cysts 3 AR 620368
Dyskeratosis Congenita Autosomal Dominant AD 127550
Dyskeratosis Congenita Autosomal Recessive AR 224230
Dyskeratosis Congenita X-Linked XL 305000
Dyskeratosis Congenita, Autosomal Dominant 4 AD 615190
Dyskeratosis congenita, autosomal dominant 6 AD 616553
Dyskeratosis Congenita, Autosomal Dominant, 2 AD 613989
Dyskeratosis Congenita, Autosomal Dominant, 3 AD 613990
Dyskeratosis Congenita, Autosomal Recessive 6 AR 616353
Dyskeratosis Congenita, Autosomal Recessive, 2 AR 613987
Dyskeratosis Congenita, Autosomal Recessive, 3 AR 613988
Melanoma, Cutaneous Malignant, 9 615134
Melanoma, Cutaneous Malignant, Susceptibility to, 10 AD 615848
Poikiloderma With Neutropenia AR 604173
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 6 AD 619767
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 AD 620365
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 8 AD 620367
Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 9 AD 620400
Pulmonary Fibrosis and/or Bone Marrow Failure, Telomere-Related, 1; PFBMFT1 AD 614742
Pulmonary Fibrosis and/or Bone Marrow Failure, Telomere-Related, 2 AD 614743
Pulmonary Fibrosis and/or Bone Marrow Failure, Telomere-Related, 3 AD 616373
Pulmonary Fibrosis and/or Bone Marrow Failure, Telomere-Related, 4 AD 616371
Pulmonary fibrosis and/or bone marrow failure, telomere-related, 5 AD 618674
Revesz Syndrome AD 268130

Related Tests

Name
PGxome®
Cerebroretinal Microangiopathy with Calcifications and Cysts (Coats plus syndrome) via the CTC1 Gene
Dyskeratosis Congenita (DC) and Hoyeraal-Hreidarsson Syndrome via the DKC1 Gene
Dyskeratosis Congenita (DC) and Revesz Syndrome via the TINF2 Gene
Inherited Bone Marrow Failure Panel
Interstitial Lung Disease Panel

Citations

  • Alder et al. 2013. PubMed ID: 23946118
  • Anderson et al. 2012. PubMed ID: 22267198
  • Briggs et al. 2008. PubMed ID: 18076099
  • Colombo et al. 2018. PubMed ID: 29770900
  • Hoyeraal et al. 1970. PubMed ID: 5442429
  • Hreidarsson et al. 1988. PubMed ID: 3201986
  • Jongmans et al. 2012. PubMed ID: 22341970
  • Kirwan et al. 2008. PubMed ID: 18005359
  • Linnankivi et al. 2006. PubMed ID: 16943371
  • Polvi et al. 2012. PubMed ID: 22387016
  • Revesz et al. 1992. PubMed ID: 1404302
  • Savage et al. 2023. PubMed ID: 20301779
  • Savage. 2022. PubMed ID: 36485133
  • Sharma et al. 2022. PubMed ID: 34767620
  • Vulliamy et al. 2006. PubMed ID: 16332973
  • Walne et al. 2007. PubMed ID: 17507419
  • Walne et al. 2010. PubMed ID: 20817924
  • Walne et al. 2016. PubMed ID: 27612988

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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