Clinical Manifestations And Gene Analysis Of Mccune-albright Sydrome

Object: Mc Cune-Albright syndrome is a rare disease,characterized by fibrous dysplasia of bone?skin cafe au lait spots and various endocrine disorders.It can affect many organs and tissues such as gonad,thyroid,pituitary and adrenal gland,etc.Most of MAS patients' clinical manifestations are atypical.The molecular mechanism of MAS is the mutation on the GNAS1 gene,which encodes the subunit ? of G protein-coupled receptor(Gs ?).The mutation is believed to occur postzygotically,leading to mosaiscism for mutation-bearing cells.These two points make the diagnosis of MAS difficult.In order to improve the precise medical treatment of MAS,we explore the clinical features and molecular mechanism of Mc Cune-Albright syndrome.Method: A total of 122 patients diagnosed as MAS were enrolled.Clinical data were obtained through detailed medical history inquiry,laboratory examination and imaging examination.Genomic DNA(from all patients' peripheral blood leukocytes)was obtained.Digital droplet PCR was used to detect the known hot mutation site of GNAS1 leading to MAS.Results: Precosious puberty is found in all the 122 patients,which is characterized by Gn RH independent precocious puberty,high estradiol,and part of them have ovarian cysts.There were 16 cases with typical triple sign,46 cases with double sign and 60 cases with combined sign.The age of premature puberty is earlier than that of children with premature thelarche or premature menarch,and the volume of uterus and ovary islarger than that of other two control groups.A total of 89 out of 123 children had improved GNAS1 gene detection,and 57 had positive results.The positive rates of dd PCR,PAP and second generation sequencing were77.4%,29% and 56.3% respectively.GNAS1 gene mutation was found in all detected classical triad patients.The positive rates of dd PCR in peripheral blood of typical and atypical children were 100% and 73.1%,respectively,which were significantly higher than those of the other two methods.The mutations of R201 C and R201 H were both positive in 22 children.The detection rate of GNAS1 mutation in precocious puberty with bone lesions was higher than that in precocious puberty with skin lesions,suggesting that fibrous dysplasia with precocious puberty is an important basis for clinical diagnosis of MAS in children.Conclusion: The most common endocrine manifestation of MAS in children is precocious puberty.Bone fibrous dysplasia with precocious puberty is an important weight factor in clinical diagnosis.The detection method of dd PCR is highly sensitive,which can be helpful for molecular diagnosis of MAS.