Mutation analysis of the follicle-stimulating hormone receptor gene in girls with gonadotropin-independent precocious puberty resulting from autonomous cystic ovaries

Objective: To search for germline activating mutations of the FSH receptor in girls with gonadotropinin-dependent precocious puberty. Design: Molecular studies in human tissue. Setting: Four girls with polycystic ovaries and gonadotropin-independent isosexual precocious puberty without clinical and molecular features of McCune-Albright syndrome. Intervention(s): Peripheral blood was used for DNA extraction. The Lu-subunit of the Ga gene and the entire exon 10 of FSH receptor gene were amplified by polymerase chain reaction (PCR). GS-alpha mutations characteristic of McCune-Albright syndrome were excluded by denaturating gradient gel electrophoresis (DGGE) and allele-specific PCR. Exon 10 of the FSH receptor gene was analyzed by DGGE and direct sequencing. Main Outcome Measure(s): Results of DGGE and direct sequencing. Result(s): No germline activating mutations were detected in exon 10 of our patients. Instead, two previously described polymorphisms were found, leading to the substitution of alanine for threonine at position 307 and of serine for asparagine at position 680 of the FSH receptor molecule. Conclusion(s): Germline activating mutations were not found in exon 10 of the FSHR gene in any of our patients. Further studies, preferably in ovarian tissue, will be required to exclude the presence of somatic activating mutations of the FSH receptor in these patients. (Fertil Steril(R) 2000;73:280-3. (C) 2000 by American Society for Reproductive Medicine.)