PRIMARY AMENORRHEA AND INFERTILITY DUE TO A MUTATION IN THE BETA-SUBUNIT OF FOLLICLE-STIMULATING-HORMONE

We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary follicle-stimulating hormone (FSH), but normal luteinizing hormone (LH) secretion. Ovulation was in duced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSHbeta-subunit gene indicated tha t she is homozygous for a two nucleotide frameshift deletion in the co ding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61-86 foll owed by a premature termination codon. The predicted truncated beta-su bunit peptide lacks regions which are important for association with t he alpha subunit and for binding to and activation of the FSH receptor . Abnormalities of FSH structure or function might be an under recogni sed but treatable cause of infertility.