Identification of allelic variants in the follicle-stimulating hormone receptor genes of females with or without hypergonadotropic amenorrhea

Objective: To determine whether women with idiopathic hypergonadotropic amenorrhea have unique alterations in the FSH receptor gene that could account for reduced activity. Design: Compare FSH receptor genes of affected women with normally menstruating control subjects. Setting: Center for Reproductive Health and university departments. Patient(s): Fourteen female subjects, including four normally menstruating controls; four sibling sisters, two of whom developed premature ovarian failure (POF); four patients with POF; one patient with 46,XX gonadal dysgenesis (GD); and one patient with hypogonadotropic hypogonadism. Intervention(s): Blood samples were collected. Main Outcome Measure(s): Restriction fragment length polymorphism (RFLP) analysis, single-stranded conformation polymorphism analysis, gel electrophoretic mobility of amplified genomic DNA, and FSH receptor gene sequence. Result(s): The DNA sequencing revealed allelic variants in one RFLP-positive control. There were two silent variants and one missense variant that resulted in a change from Asp to Gly at position 334 from the start Met in the amino acid sequence. Six of 10 subjects, including controls and patients with POF and GD, had an allelic variant in which A was changed to G at position 919 which caused Thr(307) to be changed to Ala. Conclusion(s): Allelic variants in the FSH receptor gene occur commonly in control subjects and affected patients. (Fertil Steril(R) 1998;70:326-31. (C) 1998 by American Society for Reproductive Medicine.).