NGS Skeletal Dysplasia Panel

 

Disorder Skeletal Dysplasia
Gene Name COL1A1        FGFR3
COL1A2        FLNA
COL2A1        HSPG2
COL10A1      SOX9
COMP           TRPV4
SLC26A2     
Clinical info 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 10 genes included on this panel account for more than 30 distinct clinical phenotypes. Click on the link below to see list of associated conditions for these genes.

List of Genes & Associated Clinical Phenotypes

Indications This panel may be most appropriate for patients with a non-specific presentation who do not fit the typical phenotype for a specific disorder or for a patient with clinical findings suggestive of more than one skeletal dysplasia.

For patients with a specific suspected skeletal dysplasia, 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.
Detection The current design of the skeletal dysplasia panel v2 covers the coding region for all 11 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 testing whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
Associated Tests

The following genes in this panel can also be requested as individual sequencing tests:
FGFR3
FLNA

Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.

Specimen Requirements 5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.

For prenatal specimens, we can accept chorionic villi, amniotic fluid, or cultured flasks from a CVS or amniocentesis. We are not performing any direct analysis at this time. For cultured flasks, please send 2x T25 flasks of confluent cells.
Transport The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. 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.
Turnaround time 4-6 weeks preliminary report; 8 weeks final report
Prenatal testing The panel can be performed on prenatal specimens when there are suggestive ultrasound findings of a skeletal dysplasia. Please be aware that due to the current turnaround time for this test, it is unlikely results will be available in time for families to use this information for pregnancy management. These results will be most helpful for families interested in recurrence risk 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.

CPT Codes 81479
Cost $3500

Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.
Contact For further information contact one of our This email address is being protected from spambots. You need JavaScript enabled to view it. at 1-800-473-9411.

Molecular Diagnostic Lab

The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.

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