Coffin-Siris Syndrome Panel

 

Disorders

Coffin-Siris Syndrome

Gene Names
ADNP HDAC8 PIGV SMC1A
ANKRD11 HELLS RAD21 SMC3
ARID1A KMT2A SMARCA2 SOX11
ARID1B KMT2D SMARCA4 TBC1D24
ARID2 NIPBL SMARCB1  
BTD PHF6 SMARCE1  
Clinical info This panel consists of 22 genes that have been associated with Coffin-Siris syndrome phenotypes. Features include intellectual disability and developmental delays, failure to thrive, hypotonia, short stature, and joint hyperextensibility. Characteristics facial features include wide mouth with thick lips, bushy brows and long lashes, and a wide and flat nasal bridge. Hirsutism is common although scalp hair is often sparse, and the nails on the fifth digits are typically absent or hypoplastic. Microcephaly may be present, and feeding difficulties are common. Most cases of Coffin-Siris are due to apparently de novo mutations in genes in the SWI-SNF pathway.

List of Genes and Conditions

Indications

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 Coffin-Siris syndrome panel covers the coding region for all 22 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 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

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.
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 8-10 weeks
Prenatal testing

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 $3,500

Insurance billing is available for this test. The 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.

NGS Panel Requisition Form

Please submit a completed Requisition Form with all samples.

 

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Molecular Diagnostic Lab Faculty

Clearing Div - do not delete (is not shown)