The genetics of hypogonadotropic hypogonadism.
An up-to-date review of the genetic aspects of idiopathic hypogonadotropic hypogonadism (IHH)/Kallmann syndrome (KS) is presented. Because proper development of the neuroendocrine axis must occur for normal puberty and reproductive function, gonadotropin-releasing hormone (GnRH) neuron migration is outlined first, followed by an introduction to the in vitro analysis of GnRH neuron migration. The normal hypothalamic-pituitary-gonadal (HPG) axis at different ages is discussed, along with a brief overview of normal and delayed puberty in both boys and girls. The phenotype of IHH/KS is discussed in detail, with its relation to Mendelian inheritance and chromosomal translocations. The molecular basis of IHH/KS is reviewed, with particular emphasis on the three most common genes ( KAL1, FGFR1, and GNRHR) that possess mutations in these patients. However, all other known genes for which mutations occur are also addressed briefly. The goal of this review is to provide a comprehensive discussion of IHH/KS, and to include both basic science and clinical findings that should allow a more complete understanding of hypothalamic-pituitary neuroendocrinology that is important in puberty and reproduction.
Bhagavath
Balasubramanian
B
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Layman
Lawrence C
LC
D000818:Animals; D002465:Cell Movement / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006066:Gonads / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D017436:Kallmann Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011627:Puberty / Q000235:genetics*; D011628:Puberty, Delayed / Q000235:genetics / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D011966:Receptors, LHRH / Q000235:genetics; D012729:Sex Chromosome Aberrations
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; C484844:GNRHR protein, human; D009419:Nerve Tissue Proteins; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1