A novel compound heterozygous mutation of the luteinizing hormone receptor - Implications for fertility

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

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish
Pages (from-to)787-794
Number of pages8
JournalJournal of Assisted Reproduction and Genetics
Volume31
Issue number7
DOIs
StatePublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Amphiregulin
  • Compound heterozygous
  • G protein coupled receptor
  • LHCGR mutation
  • Luteinizing hormone receptor
  • Signal peptide

ASJC Scopus subject areas

  • Reproductive Medicine
  • Genetics
  • Obstetrics and Gynecology
  • Developmental Biology
  • Genetics(clinical)

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