Skeletal Dysplasia NGS Panel

This panel of 11 genes is intended for patients with a diagnosis or clinical suspicion of skeletal dysplasia and is performed by Next Generation Sequencing (NGS).

Turnaround Time

5 weeks

CPT Code(s)

81479

Cost

$2,500

Genes

• Achondroplasia
• Arthrochalasia Ehlers-Danlos syndrome
• Pseudoachondroplasia
• Achondrogenesis type 1B
• Frontometaphyseal dysplasia
• Dyssegmental dysplasia, Silverman-Handmaker type
• Campomelic dysplasia
• AD Brachyolmia
• Metaphyseal chondrodysplasia, Schmid type

Skeletal dysplasias make up a large and diverse group of disorders. A diagnosis is often based on a combination of clinical, radiological, and molecular findings. There is a great deal of phenotypic overlap and genetic heterogeneity among skeletal dysplasias. The 11 genes included on this panel account for more than 30 distinct clinical phenotypes.

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. 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 Xon microarray. 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.

This panel can be used for prenatal samples based on abnormal skeletal findings on ultrasound. 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.