A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman with primary amenorrhea

The FSH receptor (FSHR) gene mutation are rare, but recently have been detected in several cases with primary amenorrhea. We report a 25-year-old female who had primary amenorrhea, moderately developed secondary sex characteristics and normal sized ovaries with small antral follicles. Her ovaries reacted slightly to clomiphene citrate therapy; they did not react to the ordinary dose of human menopausal gonadotropin (hMG) (150 IU/day x 69 days), but did react to high-dose hMG (300 IU/day x 6 days) treatment. These ovarian responses to hMG stimulation suggested an FSHR dysfunction of her ovaries. We extracted genomic DNA and analysed FSHR gene sequence after we obtained the written informed consent from the patient under the approval by the Ethics Committee of Yamaguchi Grand Medical Centre and the Yamaguchi University School of Medicine. Direct sequencing revealed a heterozygous mutation 662T -> G resulting in the substitution of valine for glycine at position 221 in exon8 of the FSHR extracellular domain, which was also confirmed by the PCR-RFLP method. The sequencing results also showed two SNPs, 919G -> A (Ala307Thr) and 2039G -> A (Ser680Asn), in exon10. A novel mutation in exon8 of FSHR was identified in a woman with primary amenorrhea whose ovaries reacted to high-dose hMG treatment.