NGS Overgrowth/Macrocephaly Panel

 

Disorder  Overgrowth and Macrocephaly Syndromes
Gene Names
 BRWD3  EED MED12 PTCH1
 CDKN1C  EZH2 NFIX PTEN
 CUL4B  GLI3  NSD1 RNF135
 DNMT3A GPC3 PHF6 UPF3B
Clinical info

This panel consists of 16 genes associated with various syndromic forms of overgrowth and macrocephaly due to germline mutations. Many of these disorders can present similarly making it difficult to pinpoint the specific diagnosis.  Overgrowth may be present in neonates at birth or develop at a later age.  In some cases, the patient's growth may normalize as they get older.  Additional features for many of the conditions on the panel include intellectual disability, congenital anomalies, or an increased risk for tumors.     

List of Genes and Associated Clinical Phenotypes

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 this panel covers the coding region for all 16 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

The following genes can also be ordered as an individual sequencing tests:

GPC3
GLI3
MED12
NSD1
PHF6
PTEN

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 $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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