| H00255 | |
| H番号 | H00255 |
| 名称 | 低ゴナドトロピン性性腺機能低下症 |
| 概要 | Hypogonadotropic hypogonadism (HH) or secondary hypogonadism is defined as a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels. HH may result from either absent or inadequate hypothalamic gonadotropin releasing hormone (GnRH) secretion or failure of pituitary gonadotropin secretion. HH can be congenital or acquired. Congenital HH is clinically and genetically heterogeneous. Clinically, the disorder is characterized by an absence of puberty and infertility. The genetic condition is classically divided in 2 groups based on the presence or absence of olfaction dysfunction. Around 50-60% of the affected individuals exhibit anosmia or hyposmia in association with idiopathic HH, defining Kallmann syndrome. Acquired HH can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X. |
| カテゴリ | 内分泌代謝疾患 |
| ネットワーク | nt06029(H00255) Glycosaminoglycan biosynthesis nt06323 KISS1-GnRH-LH/FSH-E2 signaling nt06361 Hypogonadotropic hypogonadism nt06526(H00255) MAPK signaling |
| 病因遺伝子 | (HH1/KAL1) ANOS1 [HSA:3730] [KO:K23413] (HH2/KAL2) FGFR1 [HSA:2260] [KO:K04362] (HH3/KAL3) PROKR2 [HSA:128674] [KO:K08380] (HH4/KAL4) PROK2 [HSA:60675] [KO:K24191] (HH5/KAL5) CHD7 [HSA:55636] [KO:K14437] (HH6/KAL6) FGF8 [HSA:2253] [KO:K04358] (HH7/FEUNS) GNRHR [HSA:2798] [KO:K04280] (HH8) KISS1R [HSA:84634] [KO:K08374] (HH9) NSMF [HSA:26012] [KO:K23844] (HH10) TAC3 [HSA:6866] [KO:K05240] (HH11) TACR3 [HSA:6870] [KO:K04224] (HH12) GNRH1 [HSA:2796] [KO:K05252] (HH13) KISS1 [HSA:3814] [KO:K23140] (HH14) WDR11 [HSA:55717] [KO:K24260] (HH15) HS6ST1 [HSA:9394] [KO:K02514] (HH16) SEMA3A [HSA:10371] [KO:K06840] (HH17) SPRY4 [HSA:81848] [KO:K17385] (HH18) IL17RD [HSA:54756] [KO:K05167] (HH19) DUSP6 [HSA:1848] [KO:K21946] (HH20) FGF17 [HSA:8822] [KO:K04358] (HH21) FLRT3 [HSA:23767] [KO:K16362] (HH22) FEZF1 [HSA:389549] [KO:K24502] (HH23/FEUNS) LHB [HSA:3972] [KO:K08521] (HH24/IFSHD) FSHB [HSA:2488] [KO:K05250] (HH25) NDNF [HSA:79625] [KO:K25687] (HH26) TCF12 [HSA:6938] [KO:K15603] (HH27) NHLH2 [HSA:4808] [KO:K09075] |
| 病原体 | - |
| 環境要因 | - |
| 発癌物質 | - |
| 治療薬 | ヒト絨毛性性腺刺激ホルモン [DR:D06457] ホリトロピンアルファ [DR:D04429] ゴナドレリン酢酸塩 [DR:D03267] |
| コメント | - |
| リンク | ICD-11: 5A61.2 ICD-10: E23.0 MeSH: D007006 D017436 C537919 OMIM: 308700 147950 244200 610628 612370 612702 146110 614837 614838 614839 614840 614841 614842 228300 614858 614880 614897 615266 615267 615269 615270 615271 616030 618841 619718 619755 |
| 文献 | PMID:18985070 著者 Dode C, Hardelin JP タイトル Kallmann syndrome. 雑誌 Eur J Hum Genet 17:139-46 (2009) DOI:10.1038/ejhg.2008.206 PMID:18987492 著者 Hardelin JP, Dode C タイトル The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. 雑誌 Sex Dev 2:181-93 (2008) DOI:10.1159/000152034 PMID:26194704 著者 Boehm U, Bouloux PM, Dattani MT, de Roux N, Dode C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, Young J タイトル Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. 雑誌 Nat Rev Endocrinol 11:547-64 (2015) DOI:10.1038/nrendo.2015.112 PMID:1594017 (ANOS1) 著者 Bick D, Franco B, Sherins RJ, Heye B, Pike L, Crawford J, Maddalena A, Incerti B, Pragliola A, Meitinger T, Ballabio A タイトル Brief report: intragenic deletion of the KALIG-1 gene in Kallmann's syndrome. 雑誌 N Engl J Med 326:1752-5 (1992) DOI:10.1056/NEJM199206253262606 PMID:12627230 (FGFR1) 著者 Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP タイトル Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. 雑誌 Nat Genet 33:463-5 (2003) DOI:10.1038/ng1122 PMID:17054399 (PROKR2 PROK2) 著者 Dode C, Teixeira L, Levilliers J, Fouveaut C, Bouchard P, Kottler ML, Lespinasse J, Lienhardt-Roussie A, Mathieu M, Moerman A, Morgan G, Murat A, Toublanc JE, Wolczynski S, Delpech M, Petit C, Young J, Hardelin JP タイトル Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. 雑誌 PLoS Genet 2:e175 (2006) DOI:10.1371/journal.pgen.0020175 PMID:18834967 (CHD7) 著者 Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC タイトル Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. 雑誌 Am J Hum Genet 83:511-9 (2008) DOI:10.1016/j.ajhg.2008.09.005 PMID:18596921 (FGF8) 著者 Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y, Jacobson-Dickman EE, Eliseenkova AV, Ma J, Dwyer A, Quinton R, Na S, Hall JE, Huot C, Alois N, Pearce SH, Cole LW, Hughes V, Mohammadi M, Tsai P, Pitteloud N タイトル Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. 雑誌 J Clin Invest 118:2822-31 (2008) DOI:10.1172/JCI34538 PMID:11397842 (GNRHR) 著者 Pitteloud N, Boepple PA, DeCruz S, Valkenburgh SB, Crowley WF Jr, Hayes FJ タイトル The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. 雑誌 J Clin Endocrinol Metab 86:2470-5 (2001) DOI:10.1210/jcem.86.6.7542 PMID:14573733 (KISS1R) 著者 Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS Jr, Shagoury JK, Bo-Abbas Y, Kuohung W, Schwinof KM, Hendrick AG, Zahn D, Dixon J, Kaiser UB, Slaugenhaupt SA, Gusella JF, O'Rahilly S, Carlton MB, Crowley WF Jr, Aparicio SA, Colledge WH タイトル The GPR54 gene as a regulator of puberty. 雑誌 N Engl J Med 349:1614-27 (2003) DOI:10.1056/NEJMoa035322 PMID:15362570 (NSMF) 著者 Miura K, Acierno JS Jr, Seminara SB タイトル Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). 雑誌 J Hum Genet 49:265-8 (2004) DOI:10.1007/s10038-004-0137-4 PMID:19079066 (TAC3 TACR3) 著者 Topaloglu AK, Reimann F, Guclu M, Yalin AS, Kotan LD, Porter KM, Serin A, Mungan NO, Cook JR, Ozbek MN, Imamoglu S, Akalin NS, Yuksel B, O'Rahilly S, Semple RK タイトル TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. 雑誌 Nat Genet 41:354-8 (2009) DOI:10.1038/ng.306 PMID:19535795 (GNRH1) 著者 Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P, Lombes M, Millar RP, Guiochon-Mantel A, Young J タイトル Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. 雑誌 N Engl J Med 360:2742-8 (2009) DOI:10.1056/NEJMoa0900136 PMID:22335740 (KISS1) 著者 Topaloglu AK, Tello JA, Kotan LD, Ozbek MN, Yilmaz MB, Erdogan S, Gurbuz F, Temiz F, Millar RP, Yuksel B タイトル Inactivating KISS1 mutation and hypogonadotropic hypogonadism. 雑誌 N Engl J Med 366:629-35 (2012) DOI:10.1056/NEJMoa1111184 PMID:20887964 (WDR11) 著者 Kim HG, Ahn JW, Kurth I, Ullmann R, Kim HT, Kulharya A, Ha KS, Itokawa Y, Meliciani I, Wenzel W, Lee D, Rosenberger G, Ozata M, Bick DP, Sherins RJ, Nagase T, Tekin M, Kim SH, Kim CH, Ropers HH, Gusella JF, Kalscheuer V, Choi CY, Layman LC タイトル WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. 雑誌 Am J Hum Genet 87:465-79 (2010) DOI:10.1016/j.ajhg.2010.08.018 PMID:21700882 (HS6ST1) 著者 Tornberg J, Sykiotis GP, Keefe K, Plummer L, Hoang X, Hall JE, Quinton R, Seminara SB, Hughes V, Van Vliet G, Van Uum S, Crowley WF, Habuchi H, Kimata K, Pitteloud N, Bulow HE タイトル Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. 雑誌 Proc Natl Acad Sci U S A 108:11524-9 (2011) DOI:10.1073/pnas.1102284108 PMID:22927827 (SEMA3A) 著者 Hanchate NK, Giacobini P, Lhuillier P, Parkash J, Espy C, Fouveaut C, Leroy C, Baron S, Campagne C, Vanacker C, Collier F, Cruaud C, Meyer V, Garcia-Pinero A, Dewailly D, Cortet-Rudelli C, Gersak K, Metz C, Chabrier G, Pugeat M, Young J, Hardelin JP, Prevot V, Dode C タイトル SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. 雑誌 PLoS Genet 8:e1002896 (2012) DOI:10.1371/journal.pgen.1002896 PMID:23643382 (SPRY4 IL17RD DUSP6 FGF17 FLRT3) 著者 Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N タイトル Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. 雑誌 Am J Hum Genet 92:725-43 (2013) DOI:10.1016/j.ajhg.2013.04.008 PMID:25192046 (FEZF1) 著者 Kotan LD, Hutchins BI, Ozkan Y, Demirel F, Stoner H, Cheng PJ, Esen I, Gurbuz F, Bicakci YK, Mengen E, Yuksel B, Wray S, Topaloglu AK タイトル Mutations in FEZF1 cause Kallmann syndrome. 雑誌 Am J Hum Genet 95:326-31 (2014) DOI:10.1016/j.ajhg.2014.08.006 PMID:19129711 (LHB) 著者 Arnhold IJ, Lofrano-Porto A, Latronico AC タイトル Inactivating mutations of luteinizing hormone beta-subunit or luteinizing hormone receptor cause oligo-amenorrhea and infertility in women. 雑誌 Horm Res 71:75-82 (2009) DOI:10.1159/000183895 PMID:8220432 (FSHB) 著者 Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambino G, Casagrande S, Tedeschini G, Benedetti A, Chatterjee VK タイトル Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. 雑誌 Nat Genet 5:83-6 (1993) DOI:10.1038/ng0993-83 PMID:31883645 (NDNF) 著者 Messina A, Pulli K, Santini S, Acierno J, Kansakoski J, Cassatella D, Xu C, Casoni F, Malone SA, Ternier G, Conte D, Sidis Y, Tommiska J, Vaaralahti K, Dwyer A, Gothilf Y, Merlo GR, Santoni F, Niederlander NJ, Giacobini P, Raivio T, Pitteloud N タイトル Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism. 雑誌 Am J Hum Genet 106:58-70 (2020) DOI:10.1016/j.ajhg.2019.12.003 PMID:32620954 (TCF12) 著者 Davis EE, Balasubramanian R, Kupchinsky ZA, Keefe DL, Plummer L, Khan K, Meczekalski B, Heath KE, Lopez-Gonzalez V, Ballesta-Martinez MJ, Margabanthu G, Price S, Greening J, Brauner R, Valenzuela I, Cusco I, Fernandez-Alvarez P, Wierman ME, Li T, Lage K, Barroso PS, Chan YM, Crowley WF, Katsanis N タイトル TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci. 雑誌 Hum Mol Genet 29:2435-2450 (2020) DOI:10.1093/hmg/ddaa120 PMID:35066646 (NHLH2) 著者 Topaloglu AK, Simsek E, Kocher MA, Mammadova J, Bober E, Kotan LD, Turan I, Celiloglu C, Gurbuz F, Yuksel B, Good DJ タイトル Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans. 雑誌 Hum Genet 141:295-304 (2022) DOI:10.1007/s00439-021-02422-9 |