title: Genetics of human hypogonadotropic hypogonadism.
abstract: Humans with hypogonadotropic hypogonadism (HH) manifest irreversible pubertal delay, infertility, and low serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Although the genetic basis of this condition is largely unknown, mutations have been identified in approximately 5-10% of HH patients. Mutations in the KAL gene (Kallmann syndrome) and the AHC gene (adrenal hypoplasia congenita/HH) cause X-linked recessive HH. Autosomal recessive HH may be brought about by mutations in the gonadotropin-releasing hormone receptor, leptin, and the leptin receptor genes. Isolated deficiencies of the gonadotropins FSH and LH are due to corresponding beta-subunit genes. PROP1 gene mutations lead to combined pituitary deficiency, and HESX gene mutations result in septo-optic dysplasia, both of which include HH. These identified gene mutations advance our understanding of normal hypothalamic-pituitary-gonadal function.
authors.affiliation: Section of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Medical College of Georgia, Augusta 30912-3360, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Layman
mesh_terms: D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins / Q000235:genetics; D016326:Extracellular Matrix Proteins; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000172:deficiency / Q000235:genetics; D005801:Genes, Homeobox; D005808:Genes, Recessive; D006062:Gonadotropins / Q000172:deficiency*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007006:Hypogonadism / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D017436:Kallmann Syndrome / Q000235:genetics; D020738:Leptin / Q000235:genetics; D007986:Luteinizing Hormone / Q000097:blood / Q000172:deficiency / Q000235:genetics; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D011966:Receptors, LHRH / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics
chemical_list: C076266:ANOS1 protein, human; D057137:DAX-1 Orphan Nuclear Receptor; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D006062:Gonadotropins; D018398:Homeodomain Proteins; D020738:Leptin; C539965:NR0B1 protein, human; D009419:Nerve Tissue Proteins; C102134:Prophet of Pit-1 protein; D011966:Receptors, LHRH; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D014157:Transcription Factors; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone