MCCUNE ALBRIGHT SYNDROME
Gene Symbol: GNAS1
Chromosomal Locus: 20q13.32
Protein: Gs-alpha protein
TURNAROUND TIME: 15 days
Primer mutagenesis polymerase chain reaction (PCR) and mutation-specific restriction enzyme digestion for mutation enrichment followed by DNA sequencing for confirmation. Due to the mosaic nature of the condition of McCune Albright Syndrome, sequencing without prior enrichment will not detect the mutation.
- Tissue: (Preferred) 15mg Affected Tissue is the preferred sample; this can either be fresh or frozen tissue. Skin tissue has a significantly lower detection rate than other affected tissues. If tissue from the affected site is not available EDTA whole blood can be used. Formalin fixed tissue is not acceptable.
- Blood Collection: Prefer two 5ml whole blood EDTA (lavender top) tube. Minimum is 0.7mls EDTA Blood. .
- Transport: fresh tissue should be transported in sterile media or sterile saline at room temperature; EDTA blood should also be sent at Room Temp. All specimens should be shipped regular next day air (No Saturday delivery, call the laboratory for specific instructions).
- Stability: Fresh Tissue 24-48 hours at room temperature; EDTA Blood - Ambient: up to 7 days; Refrigerated: 2 weeks. Frozen EDTA blood is unacceptable. Frozen Tissue is acceptable.
- Unacceptable Conditions: Serum. Frozen or severely hemolyzed blood. Clotted blood. Formalin fixed and paraffin embedded tissue.
- Prenatal testing: Prenatal testing is not recommended due to mosaic nature of the syndrome.
Counseling and informed consent are recommended for genetic testing. A consent form
is available as a resource but not required.
Inheritance: GNAS1 mutations at codon 201 in patients with the McCune-Albright syndrome are present in the mosaic state, resulting from a postzygotic somatic mutation appearing early in embryo development which produces a monoclonal population of mutated cells within variously affected tissues. The nonmosaic state for these activating mutations is presumably lethal to the embryo.
Disease Characteristics: There is a classic triad of symptoms polyostotic fibrous dysplasia, cafe-au-lait spots and/or precocious puberty. However, the symptoms are often seen in isolation depending on the pattern of organ-specific mosaicism. Other endocrine problems can also be seen in these patients.
Molecular Genetic Mechanism: Two different point mutations Arg201Cys and Arg201His have been associated with McCune Albright syndrome.
Clinical Sensitivity: Could be as high as 50% in blood, and 90% in affected tissues.
Analytical Sensitivity: 99%
Test Limitations: McCune Albright is a mosaic disorder; therefore a negative result in one tissue does not rule out disease. Skin tissue has a significantly lower detection rate than other affected tissues.
INDICATIONS FOR USE:
- Patients with a diagnosis of McCune Albright Syndrome.
- Children with precocious puberty or endocrine disorders.
- Patients with multiple cafe-au-lait spots.
- Patients with polyostotic fibrous dysplasia in bones, joints or skull.