McCune-Albright syndrome (MAS) is characterized by the triad of precocious puberty, café au lait pigmentation, and polyostotic fibrous dysplasia (FD) of bone, and is caused by post-zygotic somatic mutations-R201H or R201C-in the guanine nucleotide binding protein, alpha stimulating (GNAS) gene.
The main features of McCune-Albright are fibrous dysplasia of bone (FD), café-au-lait macules and precocious puberty; the disease is caused by activating mutations in the Guanine Nucleotide-binding protein, Alpha-stimulating activity polypeptide (GNAS) gene which are always somatic.
We performed a systematic analysis of genomic DNA for the detection of GNAS activating mutations in girls with MAS who presented with precocious puberty to evaluate whether identification of an activating mutation in peripheral blood is related to the presence of other features of MAS.
Sexual precocity has been ascribed to the occurrence of a mutant GNAS1 allele in the gonadal anlage, from which all somatic cells of the differentiated gonads arise.
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.
In humans, inactivating GPR54 mutations cause normosmic hypogonadotrophic hypogonadism whilst activation of GPR54 signalling is associated with premature puberty.
Two gain-of-function mutations of the KISS1 and KISS1R genes were implicated in the pathogenesis of GnRH-dependent precocious puberty, previously considered idiopathic.
Given that MKRN3 mutation was detected in only one patient, with a paternal history of precocious puberty, this reinforces the importance of accurate family history taking.
Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty.
The predictive value of leptin (AUC =0.791) was lower than that of IGF-1 (AUC =0.917, p = .009), although both were significant markers for PP in the regression analysis.