Next-Gen Sequencing of GNAS Only for McCune-Albright Syndrome (GNAS-NG)
Information for Ordering
{slide=Acceptable Specimen Types}
• Fresh blood sample (3-6 ml EDTA; no time limitations associated with receipt)
• Saliva (OGR-575 DNA Genotek; kits are provided upon request)
• DNA (extracted from lymphocyte cells; a minimum volume of 25μL at 3μg; O.D. of 260:280nm ≥1.8; must be extracted in a CLIA or equivalent certified lab)
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Average = 30 working days for blood, saliva, or DNA
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$700 (USD – institutional/self-pay price)
CPT: 81479
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{slide=Candidates for Testing}
Patients with abnormal CAL spots (frequently large and with irregular borders); clear polyostotic fibrous dysplasia, which may present as fractures, uneven bone growth, or deformity; and/or precocious puberty or other endocrine problems.
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Please find specimen requirement specifications above.
All submitted specimens must be sent at room temperature. DO NOT ship on ice.
Specimens must be packaged to prevent breakage and absorbent material must be included in the package to absorb liquids in the event that breakage occurs. Also, the package must be shipped in double watertight containers (e.g. a specimen pouch + the shipping company’s diagnostic envelope).
To request a sample collection kit, please click here or email medgenomics@uabmc.edu to complete the specimen request form.
Please contact the MGL (via email at medgenomics@uabmc.edu, or via phone at 205-934-5562) prior to sample shipment and provide us with the date of shipment and tracking number of the package so that we can better ensure receipt of the samples.
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Form for Customs
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About
{slide=Disorder Background} McCune-Albright syndrome is caused by variants affecting codons p. Arg201 and p.Gln227 in eons 8 and 9 GNAS and is characterized by polyostotic fibrous dysplasia, café-au-lait hyperpigmentation and precocious puberty.(Boyce AM, et al. Genereviews. 2019). Patients with McCune-Albright syndrome has mosaic GNAS variants; thus the disorder presentation is highly variable, depending on the specific tissues involved and the extent of the involvement. Part of this variability can be accounted for by the fact that pathogenic GNAS variants are not inherited, as completely affected embryos are thought to be incompatible with life, meaning that all variants occur de novo and pathogenic variants are not present in every cell in the body (mosaic). The MGL provides testing for GNAS given the overlap between segmental/mosaic NF1/Legius syndrome and McCune-Albright syndrome.
The GNAS gene codes for an alpha subunit of the stimulatory guanine nucleotide-binding protein (G protein), which is responsible for transducing extracellular signals received by transmembrane receptors in a cascade to effector proteins. The majority of all GNAS-related pathogenicity is caused by gain-of-function postzygotic somatic GNAS variants in exon 8 or 9, which leads to a constitutively active G protein. GNAS-related G protein over-activation results in the overproduction of a number of hormones associated with abnormal bone growth and other symptoms of McCune-Albright syndrome.
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The DNA-based GNAS-only by NGS involves NextGen sequencing of exons 8 and 9. The test uses an extensively customized and optimized set of Agilent HaloPlex capture probes, followed by sequencing of overlapping amplicons within the regions of interest using 300bp paired-end Illumina sequencing chemistry. Each coding exon plus ~50bp of flanking intronic sequence are simultaneously sequenced. 5’ and 3’ untranslated sequences are not included.
The average coverage of the GNAS-only by NGS for exons 8 and 9 is >1600x, allowing detection of very low level mosaicism, down to 3% variant allele fraction with 95% confidence.
REFERENCES available here.
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Other related test options:
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.
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