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Primary amenorrhoea and infertility due to a mutation in the β–subunit of follicle–stimulating hormone

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Abstract

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 induced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSHβ–subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61–86 followed by a premature termination codon. The predicted truncated β–subunit peptide lacks regions which are important for association with the α subunit and for binding to and activation of the FSH receptor. Abnormalities of FSH structure or function might be an under recognised but treatable cause of infertility.

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Authors and Affiliations

  1. Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 2QQ, UK

    C.H. Matthews, M. Adams, Y. Tone & V.K.K. Chatterjee

  2. Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Via F. Sforza 35, 20122, Milan, Italy

    S. Borgato, P. Beck-Peccoz & G. Gambino

  3. Department of Endocrinology, University of Trieste, Cattinara Hospital, 34100, Cattinara, Italy

    S. Casagrande, G. Tedeschini & A. Benedetti

Authors
  1. C.H. Matthews
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  2. S. Borgato
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  3. P. Beck-Peccoz
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  4. M. Adams
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  5. Y. Tone
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  6. G. Gambino
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  7. S. Casagrande
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  8. G. Tedeschini
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  9. A. Benedetti
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  10. V.K.K. Chatterjee
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Matthews, C., Borgato, S., Beck-Peccoz, P. et al. Primary amenorrhoea and infertility due to a mutation in the β–subunit of follicle–stimulating hormone. Nat Genet 5, 83–86 (1993). https://doi.org/10.1038/ng0993-83

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  • DOI: https://doi.org/10.1038/ng0993-83

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