Cornelia de Lange Syndrome Sequencing Panel

Test Information

This panel of 5 genes is intended for patients with a diagnosis of Cornelia de Lange Syndrome and is performed by Next Generation Sequencing (NGS). This molecular test is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Turnaround Time

8-10 weeks

CPT Code(s)

81479

Cost

$2,000

Genes

Clinical Information

Cornelia de Lange syndrome is characterized by growth retardation of prenatal onset, microcephaly, small hands and feet, limb abnormalities, and reflux. Dysmorphic features include synophrys, upturned nose, downturned mouth, and low-set ears. Long eyelashes are common as are hirsuitism and a coarsened appearance. Cleft palate, kidney abnormalities, and heart defects are present in some patients. Intellectual disability is common, and many individuals with Cornelia de Lange also experience hearing loss. Other issues may include self-injurious behaviors, obsessive-compulsive disorder, and autistic tendencies. Cornelia de Lange syndrome often results from de novo autosomal dominant mutations in NIPBL, RAD21, or SMC3, while SMC1A and HDAC8 demonstrate X-linked inheritance with both males and females exhibiting symptoms. Cornelia de Lange shows variable expressivity although individuals with NIPBL mutations tend to show more severe phenotypes.

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. All 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 this sequencing panel. The GGC Diagnostic Laboratory Directors and genetic counselors 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
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