Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes

The Journal of Clinical Endocrinology and Metabolism
Yousef Bo-AbbasS B Seminara

Abstract

Failure of the normal pattern of episodic secretion of GnRH from the hypothalamus results in the clinical syndrome of idiopathic hypogonadotropic hypogonadism (IHH), with failure of pubertal development and infertility. The only gene that has been implicated in normosmic IHH is the GnRH receptor gene (GNRHR), which accounts for 10% of cases. This report presents four families with autosomal recessive IHH, including a consanguineous pedigree from the Middle East. Defects within the genomic coding sequence of the GNRHR, and the GnRH gene itself, GNRH1, were excluded by temperature gradient gel electrophoresis, direct sequencing, and haplotypes created from simple sequence polymorphisms flanking the GNRH1 and GNRHR loci. We concluded that: 1) genetic analysis has excluded sequence variations in GNRH1 and GNRHR in four families with recessive IHH, suggesting the existence of a novel, as-yet-undiscovered gene for this condition, and 2) because mutation analysis of genomic coding sequence will fail to detect mutations deep within introns or regulatory regions, haplotype analysis is the preferred genetic methodology to eliminate the role of specific candidate genes.

Associated Clinical Trials

Citations

Jul 13, 2007·Pituitary·Ericka Barbosa TrarbachAna Claudia Latronico
Mar 6, 2007·Reviews in Endocrine & Metabolic Disorders·Felecia Cerrato, Stephanie B Seminara
Oct 24, 2003·The New England Journal of Medicine·Stephanie B SeminaraWilliam H Colledge
Jun 19, 2009·The New England Journal of Medicine·Jérôme BouligandJacques Young
Nov 11, 2011·The Journal of Clinical Endocrinology and Metabolism·Hilana M Lewkowitz-ShpuntoffRavikumar Balasubramanian
Mar 9, 2010·European Journal of Endocrinology·Frédéric BrioudeJacques Young
Jun 3, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Elena Gianetti, Stephanie Seminara
Jun 18, 2014·The Journal of Clinical Investigation·Stephanie B Seminara
Jan 10, 2012·International Journal of Endocrinology·Karges BeateKarges Wolfram
Jul 5, 2011·Molecular and Cellular Endocrinology·Yee-Ming Chan
Jun 28, 2011·Molecular and Cellular Endocrinology·Fazal WahabStephanie B Seminara
Jul 23, 2008·Peptides·Yee-Ming ChanStephanie B Seminara
Feb 10, 2009·Annales d'endocrinologie·C RozeN de Roux
Jun 26, 2015·Birth Defects Research. Part C, Embryo Today : Reviews·Kathleen E Whitlock
Oct 26, 2005·Animal Reproduction Science·C L LinK Wimmers
Nov 12, 2018·Journal of Neuroendocrinology·Silvia Regina Correa-SilvaMagnus R Dias-da-Silva
Feb 15, 2019·Frontiers in Endocrinology·Prashantha HebbarThangavel Alphonse Thanaraj

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