Dyskeratosis Congenita NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81479

Cost

$2,500

Genes

• Dyskeratosis congenita
• LIG4 syndrome
• Telomere-related Pulmonary fibrosis and/or bone marrow failure
• Poikiloderma with neutropenia
• Ectodermal Dysplasia/Short Stature syndrome
• Dubowitz syndrome
• Idiopathic pulmonary fibrosis

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.

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.

Next Generation Sequencing

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.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

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.

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.