Abstract

Objective To identify GNAS1 gene mutations in girls with exaggerated and/or chronic fluctuating thelarche for at least 1-year duration with no other signs of precocious puberty, skeletal dysplasia, or typical skin lesions of McCune-Albright syndrome. Study design We studied the GNAS1 gene mutation by allele-specific polymerase chain reaction and enzymatic digestion in leukocyte DNA in 23 girls previously described. Results Fluctuating thelarche was present in 14 girls and exaggerated thelarche was observed in 9. Molecular study revealed that 6 girls had a substitution of arginine by histidine in codon 201 (R201H [+]). Three R201H (+) girls reached their menarche at a mean chronologic age of 10.8 years and 9 of the R201H (-) girls at a mean age of 11 years. Conclusions Activating mutations of GNAS1 gene may be observed in some girls with chronic fluctuating and/or exaggerated thelarche, without other classic signs of McCune-Albright syndrome.