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A novel compound heterozygous mutation of the luteinizing hormone receptor –implications for fertility

  • Gonadal Physiology and Disease
  • Published:
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Abstract

The luteinizing hormone/chorionic gonadotropin receptor (LHCGR) belongs to the family of G-protein coupled receptors and binds both luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Ligand-receptor interaction mediates a downstream cascade of events which is essential for ovulation in women, and expression of the male phenotype in men. The human LHCGR gene consists of 11exons and 10 introns. Homozygous and compound heterozygous mutations may inactivate the receptor by altering its structure and subsequent function. Herein we reported a novel, compound heterozgygous inactivating LHCGR mutation in a woman who presented with secondary infertility, having previously carried to term a donor oocyte pregnancy. A 27 bp deletion was detected in exon I at amino acid number 12. This mutation involved the signal peptide region, which is important for protein targeting, maturation and cellular expression. Another mutation involving a 2 base pair (thymine and cytosine) deletion was detected in exon 11 at amino acid number 586. This deletion produced a frameshift resulting in a premature stop codon and a truncated protein. An XY sibling with the same mutations was phenotypically female and misdiagnosed as complete androgen insensitivity syndrome. Other unaffected family members were genetically tested and carried one of the two mutations.

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Authors and Affiliations

  1. Toronto Center for Advanced Reproductive Technology (TCART), Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 150 Bloor Street West, Suite 210, Toronto, ON, M5S 2X9, Canada

    Frederic Mitri, Yaakov Bentov, Lucy Ann Behan, Navid Esfandiari & Robert F. Casper

Authors
  1. Frederic Mitri
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  2. Yaakov Bentov
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  3. Lucy Ann Behan
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  4. Navid Esfandiari
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  5. Robert F. Casper
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Corresponding author

Correspondence to Robert F. Casper.

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Capsule A novel compound heterozygous mutation involving exon 1 and 10 resulting in LH/hCG resistance, infertility and female phenotype in XY and XX siblings.

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Mitri, F., Bentov, Y., Behan, L.A. et al. A novel compound heterozygous mutation of the luteinizing hormone receptor –implications for fertility. J Assist Reprod Genet 31, 787–794 (2014). https://doi.org/10.1007/s10815-014-0249-5

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  • DOI: https://doi.org/10.1007/s10815-014-0249-5

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