Dyskeratosis Congenita Sequencing Panel

Test Information

Turnaround Time

8-10 weeks

CPT Code(s)

81479

Cost

$2500

Genes

Clinical Information

The panel consists of 14 genes associated with dyskeratosis congenita. This group of conditions is mostly inherited in an autosomal dominant or autosomal recessive pattern, but one gene (DKC1) is inherited as an X-linked recessive disorder. Patients may present with IUGR, failure to thrive, or short stature. Ectodermal features include nail dystrophy, dental anomalies and caries, sparse hair and lashes, premature graying, and skin rashes or pigmentation such as poikiloderma. Leukoplakia, or white patches on mucosal tissue, may be present in some forms of the disorder. Hematologic findings may include anemia, neutropenia, leukopenia, and bone marrow failure or myelodysplastic syndrome. Dilated cardiomyopathy occurs in some types, and gastrointestinal symptoms, kidney abnormalities, and eye findings may be present. Developmental delays may occur, and affected individuals may be at risk for osteoporosis. Recurrent infections are common, and pulmonary fibrosis can occur.

Indications

For patients with a specific suspected disorder, individual gene sequencing should be considered first.

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Methodology

Next Generation Sequencing

Detection

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. Novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations, and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts.

We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray to complement the sequencing. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

Specimen Requirements

5 to 7 ml of peripheral blood collected in an EDTA (lavender top) tube is the preferred specimen type. The minimal blood needed for reliable DNA isolation is 3 ml. Extracted DNA is also accepted for this test.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal Testing Information

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

Have Questions Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Kellie Walden, MS, CGC

Molecular Testing, NGS Panel, NGS Panels
Meet the Shenal Family

Meet the Shenal Family

Our daughter, Ryleigh, was diagnosed with a rare chromosomal deletion shortly after she was born in 2010. Since we received her diagnosis, the Greenwood Genetic Center has become part of our family. They made certain that we did not feel alone, and they continue to provide ongoing, compassionate care for our child. The impact they have had on our family and others across the globe everyday is immeasurable. We can't imagine walking this journey without their...

In The News