Invitae Dyskeratosis Congenita Panel


Test description

This test analyzes seven genes that are associated with dyskeratosis congenita (DC). DC is a clinically and genetically heterogeneous telomere biology disorder characterized by abnormal skin pigmentation, nail dystrophy, oral leukoplakia, and increased risk of progressive bone marrow failure and development of malignancies.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.

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Primary panel (7 genes)


Alternative tests to consider

These genes can also be ordered as part of broader panels. Depending on the individual’s clinical and family history, one of these panels may be appropriate and can be ordered at no additional charge.

Dyskeratosis congenita

DC is a telomere biology disorder and is classically characterized by dysplastic nails, lacy reticular pigmentation, and oral leukoplakia. Reduced penetrance is common, so some individuals might not have these symptoms. Individuals with DC have an increased risk of progressive bone marrow failure, myelodysplastic syndrome, acute myelogenous leukemia, solid tumors, and pulmonary fibrosis. These symptoms may be the presenting features in some individuals. Other findings can include abnormal pigmentation changes, eye abnormalities, and dental anomalies. The age of onset is variable and disease presentation can be mild to severe.
Individuals with pathogenic variants in the CTC1 gene may have additional symptoms, including leukoencephalopathy, brain calcifications, and cysts.

A pathogenic variant has been identified in approximately 50% of individuals who meet the clinical diagnostic criteria for DC.

GeneAttribution to DC
CTC1 1%–3%
DKC1 17%–36%
NHP2 <1%
NOP10 <1%
TERC 6%–10%
TERT 1%–7%
TINF2 11%–24%

The inheritance of DC varies by gene:

  • autosomal dominant: TERC, TINF2
  • autosomal recessive: CTC1, NHP2, NOP10
  • autosomal dominant or autosomal recessive: TERT
  • X-linked: DKC1

The clinical expression of DC is widely variable, even among family members, and the exact penetrance is unclear. However, abnormally short telomeres have been consistently demonstrated in individuals with pathogenic variants in causative genes, regardless of clinical phenotype.

The prevalence is unknown.

Testing for DC should be considered in individuals with a personal history of:

  • clinical features of DC (particularly dysplastic nails, lacy reticular pigmentation, and oral leukoplakia)
  • progressive bone marrow failure at any age
  • myelodysplastic syndrome or acute myeloid leukemia presenting at a younger age than usually found
  • solid tumors of the head, neck, or anogenital area in individuals <50 years old
  • pulmonary fibrosis
  • shortened telomere length
  • a family history of DC

If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.

Clinical management of DC patients is complex and requires comprehensive coordinated care among specialties. Recommendations for management have been discussed at a DC clinical research workshop held at the NIH in 2008:

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CTC1 NM_025099.5
DKC1 NM_001363.4
NHP2 NM_017838.3
NOP10 NM_018648.3
TERC NR_001566.1
TERT NM_198253.2
TINF2 NM_001099274.1