Partial hypogonadotropic hypogonadism associated with the Leu2665Arg and Gln106Arg mutation of the gonadotropin-releasing hormone receptor

We describe a patient with partial hypogonadotropic hypogonadism caused by a compound heterozygous GnRH-R mutation. She is a 20 year-old tall, eunuchoid female referred for evaluation of primary amenorrhea. Spontaneous thelarche occurred at the age of 15 years. Breast and pubic hair were at Tanner stages 3 and 4, respectively. Evaluation revealed low plasma estradiol level and absence of withdrawal bleeding after progestin challenge. Pelvic ultrasonography showed a small uterus and ovaries. Bone age was delayed at 14.5 years. Bone mineral density showed osteopenia. Endogenous LH secretory pattern was abnormal with low amplitude and frequency, but responded to pulsatile GnRH administration. The coding exons of the GnRH-R gene were amplified and the PCR products were sequenced bidirectionally. Two different mutations were identified: one in exon 1 (Gln106Arg) and the other in exon 3 (Leu266Arg).