{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"contact_person":["Nelly Pitteloud"],"full_dataset_link":["https://ega-archive.org/dacs/EGAC00001000690"],"host":["EGA"],"description":["EGA DAC EGAC00001000690"],"repository":["EGA"],"email":["nelly.pitteloud@chuv.ch"],"pubmed_abstract":["Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic form of isolated gonadotropin-releasing hormone (GnRH) deficiency caused by mutations in > 30 genes. Fibroblast growth factor receptor 1 (<i>FGFR1</i>) is the most frequently mutated gene in CHH and is implicated in GnRH neuron development and maintenance. We note that a CHH <i>FGFR1</i> mutation (p.L342S) decreases signaling of the metabolic regulator FGF21 by impairing the association of FGFR1 with β-Klotho (KLB), the obligate co-receptor for FGF21. We thus hypothesized that the metabolic FGF21/KLB/FGFR1 pathway is involved in CHH Genetic screening of 334 CHH patients identified seven heterozygous loss-of-function <i>KLB</i> mutations in 13 patients (4%). Most patients with <i>KLB</i> mutations (9/13) exhibited metabolic defects. In mice, lack of <i>Klb</i> led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Peripheral FGF21 administration could indeed reach GnRH neurons through circumventricular organs in the hypothalamus. We conclude that FGF21/KLB/FGFR1 signaling plays an essential role in GnRH biology, potentially linking metabolism with reproduction."],"pubmed_title":["&lt;i&gt;KLB&lt;/i&gt;, encoding β-Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism."],"pubmed_authors":["Xu Cheng C, Messina Andrea A, Somm Emmanuel E, Miraoui Hichem H, Kinnunen Tarja T, Acierno James J, Niederländer Nicolas J NJ, Bouilly Justine J, Dwyer Andrew A AA, Sidis Yisrael Y, Cassatella Daniele D, Sykiotis Gerasimos P GP, Quinton Richard R, De Geyter Christian C, Dirlewanger Mirjam M, Schwitzgebel Valérie V, Cole Trevor R TR, Toogood Andrew A AA, Kirk Jeremy Mw JM, Plummer Lacey L, Albrecht Urs U, Crowley William F WF, Mohammadi Moosa M, Tena-Sempere Manuel M, Prevot Vincent V, Pitteloud Nelly N"],"name_synonyms":["fbwd4, l(2)04454, DmelCG1772, dac, grupo, CIB1, ensemble, shsf3, shfm3, Rest, E(Sev-CycE)2B, p21[dacapo], Fbw4, FBW4, dactylin, E130112M23Rik, Dach, CDKN2B, cdi4, set, SHFM3, Dac, DAC, p27[Dap], grupos, dactylyn, dacapo/cyclin-dependent kinase interactor 4, AI182278, p21, CG1772, FBWD4, Dap, group., Cdi4, CDI4, CES5A1, p27, P15, fbw4, SHSF3, Decapo, groupe, Gruppe"],"pubmed_title_synonyms":["BKL, AV071179, Client., Patient, Clients, betaKlotho"],"pubmed_abstract_synonyms":["biochemical pathways, Forms, Metabolic Process, Materials, Laboratory, lambdatop, HBGFR, Mus domesticus, Metabolic Concepts, Receptors, dFGFR, chh-a, dev, CASP-14, Human Reproductive Indexes, Lamina Terminalis, FGF-21, House Mouse, betaKlotho, CD331, Mutations, x1fgfr, CEK, Roles, Biological, Associations, DFGF-R1, Biorhythm, Concepts, Eask, Biorhythms, Metabolism Concept, Circumventricular Organs, Phenomenon, FGF Receptor, Btl, DFR2, Fgf-r, FLG, Human Reproductive Index, cek, Gnrh2, Biological Rhythms, catabolism, LHFSH, Swiss Mice, Hspy, metabolic process resulting in cell growth, fgfr-1, Pubertal delay, Dfr-2, Rgnrhg1, FGF Receptor Complexes, Sub-Fertility, hpg, genetic, Releasing Hormone, flg, BTL/FGFR2, Gonadotropin Releasing Hormone, LH FSH Releasing Hormone, dhh, Luteinizing Hormone-Releasing Hormone, Rhythms, Role Concepts, reproductive physiological process, Periods, biotransformation, Gonadorelin, Bioperiodicity, LH-RH, Nerve Cell, Tk2, Catabolism, Flt-2, single organism signaling, CHH, Indices, Process, Index, metabolism resulting in cell growth, familial, LHRH, mouse, Fibroblast Growth Factor Receptors, bFGF-R-1, Gnrha, Sensory, Delayed pubertal development, Fgfr-1, chh, Reproductive Index, Gn-RH, Heparin-Binding Growth Factor Receptor, Role Concept, XFGFR-1, Rhythmicity, dhh-A, Human Reproductive Indices, Reproductive Periods., Factrel, Mini-ICE, Areas, Role, Genetic Materials, Area, secretion, regulator, dhh-1, GRH, Genetic Material, Preoptico-Hypothalamic, Mus musculus, Neurohemal, Nerve Cells, Mckusick type, Caspase-14 subunit p10, Sensory Circumventricular Organs, DmelCG32134, FGFR-1, GnRH-secreting neuron, mice, Swiss Mouse, Luliberin, INSDC_feature:gene, Caspase-14 subunit p19, XFGFRA2, MICE, Dirigestran, domesticus, Gonadoliberin, Patient, Material, c-fgr, Cells, Rhythmicities, Delayed Puberty, Biological Rhythm, Cistron, inherited genetic, Mouse, l(3)00208, Lhrh, LH Releasing Hormone, HH12, 3.4.22.-, Sensory Circumventricular, Bioperiodicities, Preoptico-Hypothalamic Area, GnRH neuron, HRTFDS, Processes, Periodicities, Nerve, FSH-Releasing Hormone, LFRH, Gene, mini-ICE, FSH Releasing Hormone, Metabolic Processes, LNRH, Circumventricular Organ, Kryptocur, KAL2, Human, BKL, Subfertility, Heparin Binding Growth Factor Receptor, Circumventricular, House, Neurohemal Organs, Metabolism, kal2, Mus musculus domesticus, HH2, hh4, Mice, Metabolism Phenomena, bfgfr, metaphyseal chondrodysplasia McKusick type, flt-2, 0844/01, Genetic, fgfr1, Swiss, Cystorelin, BFGFR, FGFBR, Metabolic Concept, Delayed pubertal growth, Maintenances, X1FGFR, GnRH, Gnrh, Reproductive Indices, CG6714, FGF21, Xchh, Rhythm, Clients, Luteinizing Hormone Releasing Hormone, FGFR, OGD, Reproductive Sterility, Neuron, LH-FSH Releasing Hormone, AV071179, LHFSH Releasing Hormone, Secretory Circumventricular Organ, AW208770, constitutitional genetic, Secretory, Human Reproductive, GNRH, Lnrh, x-chh, Gonadorelin Acetate, FGFR1, Organ, Reproductive, FLT2, FGF Receptors, 5-oxoPro-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 (human or pig), degradation, ogd, FLT-2, Preoptico-Hypothalamic Areas, Reproductive Period, D-FGFR, Cyclicity, function, dtk2, Cistrons, Client, Cell, xfgfr1, N-SAM, Concept, Metabolic Phenomena, LHFSHRH, Metabolism Concepts, FGF, fgf-r, Period, Mus, DmHD-311, Gonadorelin Hydrochloride, Phenomena, metaphyseal chondrodysplasia, flt2, rare (European definition), metabolism, Metabolic Phenomenon, Lhrh1, multicellular organism metabolic process, biodegradation, Metabolic, Neurohemal Organ, Preoptico Hypothalamic Area, House Mice, Delayed puberty, MFR, Laboratory Mice, CG32134, CT20816, Sensory Circumventricular Organ, Secretory Circumventricular, cartilage hair hypoplasia like syndrome, Organs, signalling process, Indexes, Sterility, Cyclicities, HD-311, LH-Releasing Hormone, Fibroblast Growth Factor Receptor, FGF Receptor Complex, Receptor, Dtk2, hereditary, Secretory Circumventricular Organs, Laboratory Mouse, hypothalamus, Anabolism"],"additional_accession":[]},"is_claimable":false,"name":"DAC for Pitteloud group","description":"Data Access Committee EGAC00001000690","dates":{"output":"2025-1-9"},"accession":"EGAC00001000690","cross_references":{"TAXONOMY":["9606"],"pubmed":["28754744"],"EGA":["EGAS00001002568","EGAD00001003463"]}}