Next-Generation Sequencing of GNAS Only for McCune-Albright Syndrome (GNAS-NG)
Information for Ordering
Acceptable Specimen Types
- Fresh blood sample: 3–6 mL EDTA; no time limitations associated with receipt
- Saliva: OGD-575 DNA Genotek collection kit; kits are provided upon request
- DNA extracted from lymphocyte cells: minimum volume of 25 µL containing 3 µg of DNA; A260/A280 ratio ≥1.8; must be extracted in a CLIA-certified or equivalent laboratory
Turnaround Time
Average turnaround time: 30 working days for blood, saliva, or DNA specimens
Price, CPT Code, and Z Code
- Institutional/self-pay price: $700 USD
- CPT code: 81479
- Z code: Z05PC
Candidates for Testing
Patients with clinical features suggestive of McCune-Albright syndrome, including abnormal café-au-lait macules that are often large and have irregular borders; polyostotic fibrous dysplasia that may present as fractures, uneven bone growth, or deformity; precocious puberty; or other endocrine abnormalities.
Specimen Shipping and Handling
Please refer to the specimen requirements listed above.
All submitted specimens must be shipped at room temperature. Do not ship specimens on ice.
Specimens must be packaged to prevent breakage. Absorbent material must be included to contain liquids if breakage occurs. Specimens must also be shipped in double watertight containers, such as a specimen pouch placed inside the shipping company’s diagnostic envelope.
To request a collection kit, please complete the Collection Kit Request Form .
Before shipping a specimen, please contact the UAB Medical Genomics Laboratory by email at medgenomics@uabmc.edu or by phone at 205-934-5562. Please provide the shipment date and package tracking number so the laboratory can help ensure proper and timely receipt.
Required Forms
About
Disorder Background
McCune-Albright syndrome is caused by variants affecting codons p.Arg201 and p.Gln227 in exons 8 and 9 of GNAS. The condition is characterized by polyostotic fibrous dysplasia, café-au-lait hyperpigmentation, and precocious puberty.
Patients with McCune-Albright syndrome have mosaic GNAS variants. Clinical presentation is therefore highly variable and depends on the specific tissues involved and the extent of involvement. Pathogenic GNAS variants are not inherited because fully affected embryos are thought to be incompatible with life. The variants arise de novo after fertilization and are not present in every cell of the body.
The UAB Medical Genomics Laboratory offers GNAS testing because of the clinical overlap between McCune-Albright syndrome and segmental or mosaic NF1 or Legius syndrome.
The GNAS gene encodes an alpha subunit of the stimulatory guanine nucleotide-binding protein, or G protein. This protein helps transmit extracellular signals received by transmembrane receptors to downstream effector proteins.
Most disease-associated GNAS variants are gain-of-function postzygotic somatic variants in exon 8 or 9. These variants result in constitutive activation of the G protein and overproduction of hormones associated with abnormal bone growth and other features of McCune-Albright syndrome.
Test Description
The DNA-based GNAS-only NGS test includes next-generation sequencing of exons 8 and 9.
The test uses a customized and optimized set of Agilent HaloPlex capture probes, followed by sequencing of overlapping amplicons within the regions of interest using 300 bp paired-end Illumina sequencing chemistry. Each coding exon plus approximately 50 bp of flanking intronic sequence is simultaneously sequenced. The 5′ and 3′ untranslated regions are not included.
Average coverage of exons 8 and 9 is greater than 1,600×, permitting detection of low-level mosaicism down to approximately 3% variant allele fraction with 95% confidence.
View references for this testing .
Other Related Test Options
For more information, test requisition forms, or collection kits, please contact the UAB Medical Genomics Laboratory at 205-934-5562 or medgenomics@uabmc.edu.