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Case Reports
. 2016 Aug 20;14(1):48.
doi: 10.1186/s12958-016-0183-8.

Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes

Nikolay Zernov  1 , Mikhail Skoblov  1   2   3 , Ancha Baranova  4   5   6   7 , Konstantin Boyarsky  8   9
Affiliations
Case Reports

Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes

Nikolay Zernov et al. Reprod Biol Endocrinol. .

Abstract

Background: Anomalous levels of gonadotropin-releasing hormone (GnRH) secretion result in a variety of reproductive phenotypes associated with infertility or subfertility. The normosmic isolated hypogonadotropic hypogonadism (nIHH) is due to a failure of either GnRH pulsatile secretion in hypothalamus or its reception in pituitary. The spectrum of nIHH-associated alterations continues to expand, especially when additional ethnic populations are investigated. The aim of this study was to uncover genetic causes for nIHH in patients of Russian origin.

Methods: For two nIHH patients referred to infertility clinic, both exons and promoter sequences of 6 GnRH signaling genes were sequenced.

Results: Patient 1 was a compound heterozygote for mutations in GnRH and its receptor encoding genes, while in Patient 2 GnRHR mutations were found in homozygous state. In both patients, the coding frame of GnRHR gene harbored missense-mutation Arg139His previously described as founder mutation in Polish and Brazilan patients. IVF/ET treatments were successful, with phenotypically healthy offsprings delivered.

Conclusion: Polish founder mutation Arg139His in GnRHR was found in two nIHH patients originating from Western region of Russia. Common variant of GnRH-encoding gene, Trp16Ser, could possibly contribute to reproductive phenotypes in patients with heterozygous mutations of other GnRH signaling pathway genes.

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Figures

Fig. 1
Fig. 1
Sanger sequencing chromatograms of mutated loci in patients and their family members. a Sequencing chromatogram of the exon 1 of GNRH1 gene in Patient 1 and Patient 2 genomes. b Sequencing chromatogram of the exon 1 of GNRHR gene in Patient 1 and Patient 2 genomes. c Sequencing chromatogram of the exon 3 of GNRHR gene in Patient 1 genomes. d Sequencing chromatogram of the exon 1 of GNRHR gene in the genomes of mothers of Patient 1 and Patient 2. e Sequencing chromatogram of the exon 1 of GNRHR gene in the genome of Patient 1 offspring
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