Table 1.

Molecular Genetic Testing Used in Fibrous Dysplasia / McCune-Albright Syndrome

Gene 1MethodVariants DetectedProportion of Probands with a Pathogenic Variant 2 Detectable by Method
GNAS Targeted analysis of exons 8 & 9 in affected tissue 3,4p.Arg201His, p.Arg201Cys 5, 6
  • 8%-90% 7
  • 75%-100% 8
p.Gln227Leu 6<5% 5
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Targeted analysis may be performed by sequence analysis. Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. For issues to consider in interpretation of sequence analysis results, click here.

4.

Testing tissue from a lesion biopsy has a higher clinical yield than testing a blood sample. The detection rate for a blood sample is ~20%-30% [Lumbroso et al 2004, Kalfa et al 2006].

5.

Somatic GNAS missense variants in individuals with FD/MAS are known to occur at only one of two amino acid residues: p.Arg201 (>95% of pathogenic variants) [Lumbroso et al 2004] or p.Gln227 (<5%) [Idowu et al 2007].

6.

Rarely, other amino acid substitutions at p.Arg201 and at p.Gln227 have been detected (see Molecular Genetics).

7.

Variant detection depends on the level of mosaicism in the tissue and the sensitivity of the technique. Variant detection at p.Arg201 using standard PCR was highest in endocrine organs and lowest in affected skin specimens [Lumbroso et al 2004].

8.

When modified primers (peptide nucleic acid) [Bianco et al 2000] and next-generation sequencing [Narumi et al 2013] technologies are combined [Narumi et al 2013], a p.Arg201 variant can be detected in virtually all affected tissues and in leukocytes in up to 75% of individuals.

From: Fibrous Dysplasia / McCune-Albright Syndrome

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