Details of Disease

Disease Name

Hypogonadotropic hypogonadism 7 with or without anosmia

HH7; hypogonadism, isolated hypogonadotropic; idiopathic hypogonadotropic hypogonadism; hypogonadotropic hypogonadism 7 without anosmia; hypogonadotropic hypogonadism 7 with or without anosmia

Definition

A hypogonadotropic hypogonadism that has material basis in homozygous or compound heterozygous mutation in the GNRHR gene on chromosome 4q13, sometimes in association with mutation in another gene. No patients with anosmia have been reported.

Disease Hierarchy

DISEV092: Congenital hypogonadotropic hypogonadism

DISPBWEU: Hypogonadotropic hypogonadism 7 with or without anosmia

Disease Identifiers

MONDO ID

MONDO_0007794

MESH ID

C562785

UMLS CUI

C0342384

OMIM ID

146110

MedGen ID

87440

SNOMED CT ID

123953004

General Information of Disease (ID: DISPBWEU)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PROKR2	TTM67AX	moderate	Genetic Variation	[1]
TACR3	TTBPGLU	moderate	Altered Expression	[2]
AXL	TTZPY6J	Strong	Genetic Variation	[3]
FGF8	TTIUF3J	Strong	Genetic Variation	[4]
FGFR1	TTRLW2X	Strong	Genetic Variation	[4]
GNRHR	TT8R70G	Strong	Autosomal recessive	[5]
KISS1	TTU2O6T	Strong	Genetic Variation	[6]
KISS1R	TT3KBZY	Strong	Genetic Variation	[7]
NELL1	TT7H4BF	Strong	Biomarker	[8]
P2RY12	TTZ1DT0	Strong	Biomarker	[9]
TACR3	TTBPGLU	Strong	Autosomal recessive	[10]
FGFR1	TTRLW2X	Definitive	Autosomal dominant	[11]
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⏷ Show the Full List of 12 DTT(s)

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
HS6ST1	OTABV7D2	moderate	Genetic Variation	[12]
SERPINA4	OTBK0GG7	moderate	Genetic Variation	[13]
SRA1	OTYOGMTG	moderate	Genetic Variation	[14]
ANOS1	OTZJT4KN	Strong	Biomarker	[15]
CCDC141	OTQ9HA3I	Strong	Genetic Variation	[16]
CHD7	OTHNIZWZ	Strong	Genetic Variation	[17]
EMX1	OT7NG5MJ	Strong	Genetic Variation	[18]
FGF17	OTAQSFZ2	Strong	Genetic Variation	[4]
GNRHR	OTLE25K3	Strong	Autosomal recessive	[5]
HESX1	OT5E2Z4G	Strong	Genetic Variation	[19]
IHH	OT1DWGXC	Strong	Genetic Variation	[20]
NDN	OTYBYJ82	Strong	Genetic Variation	[21]
NSMF	OTLTA24A	Strong	Genetic Variation	[22]
PLXNA1	OTN0BING	Strong	Genetic Variation	[20]
PROK2	OT70IFEZ	Strong	Biomarker	[23]
SIX6	OTD1RD9D	Strong	Biomarker	[24]
TAC3	OTOJGM38	Strong	Autosomal recessive	[10]
TACR3	OT7Q68XE	Strong	Autosomal recessive	[10]
DDOST	OT39PDMS	Definitive	Genetic Variation	[25]
FGFR1	OT4GLCXW	Definitive	Autosomal dominant	[11]
MCF2L	OTEURA8N	Definitive	Genetic Variation	[25]
SEMA7A	OT0ZJK64	Definitive	Biomarker	[26]
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⏷ Show the Full List of 22 DOT(s)

References

1	PROKR2 mutations in idiopathic hypogonadotropic hypogonadism: selective disruption of the binding to a G-protein leads to biased signaling.FASEB J. 2019 Mar;33(3):4538-4546. doi: 10.1096/fj.201801575R. Epub 2018 Dec 21.
2	Responsiveness to a physiological regimen of GnRH therapy and relation to genotype in women with isolated hypogonadotropic hypogonadism.J Clin Endocrinol Metab. 2013 Feb;98(2):E206-16. doi: 10.1210/jc.2012-3294. Epub 2013 Jan 22.
3	Functional consequences of AXL sequence variants in hypogonadotropic hypogonadism.J Clin Endocrinol Metab. 2014 Apr;99(4):1452-60. doi: 10.1210/jc.2013-3426. Epub 2014 Jan 29.
4	Genotypic and phenotypic spectra of FGFR1, FGF8, and FGF17 mutations in a Chinese cohort with idiopathic hypogonadotropic hypogonadism.Fertil Steril. 2020 Jan;113(1):158-166. doi: 10.1016/j.fertnstert.2019.08.069. Epub 2019 Nov 17.
5	Resistance of hypogonadic patients with mutated GnRH receptor genes to pulsatile GnRH administration. J Clin Endocrinol Metab. 1999 Mar;84(3):990-6. doi: 10.1210/jcem.84.3.5518.
6	Understanding the functions of kisspeptin and kisspeptin receptor (Kiss1R) from clinical case studies.Peptides. 2019 Oct;120:170019. doi: 10.1016/j.peptides.2018.09.007. Epub 2018 Oct 16.
7	Three Siblings with Idiopathic Hypogonadotropic Hypogonadism in a Nonconsanguineous Family: A Novel KISS1R/GPR54 Loss-of-Function Mutation.J Clin Res Pediatr Endocrinol. 2019 Nov 22;11(4):444-448. doi: 10.4274/jcrpe.galenos.2019.2018.0230. Epub 2019 Mar 25.
8	Nell-1 Is a Key Functional Modulator in Osteochondrogenesis and Beyond.J Dent Res. 2019 Dec;98(13):1458-1468. doi: 10.1177/0022034519882000. Epub 2019 Oct 14.
9	G protein-coupled receptor mutations and human genetic disease.Methods Mol Biol. 2014;1175:153-87. doi: 10.1007/978-1-4939-0956-8_8.
10	TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009 Mar;41(3):354-358. doi: 10.1038/ng.306. Epub 2008 Dec 11.
11	Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. doi: 10.1038/ng1122. Epub 2003 Mar 10.
12	Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11524-9. doi: 10.1073/pnas.1102284108. Epub 2011 Jun 23.
13	Mutation analysis of the KAL gene in female patients with gonadotropin-releasing hormone deficiency.Yonsei Med J. 2004 Feb 29;45(1):107-12. doi: 10.3349/ymj.2004.45.1.107.
14	Idiopathic Hypogonadotropic Hypogonadism Caused by Inactivating Mutations in SRA1.J Clin Res Pediatr Endocrinol. 2016 Jun 5;8(2):125-34. doi: 10.4274/jcrpe.3248. Epub 2016 Apr 18.
15	Exogenous kisspeptin administration as a probe of GnRH neuronal function in patients with idiopathic hypogonadotropic hypogonadism.J Clin Endocrinol Metab. 2014 Dec;99(12):E2762-71. doi: 10.1210/jc.2014-2233.
16	CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1816-1825. doi: 10.1210/jc.2016-3391.
17	Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort.J Clin Endocrinol Metab. 2020 May 1;105(5):dgz182. doi: 10.1210/clinem/dgz182.
18	WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2010 Oct 8;87(4):465-79. doi: 10.1016/j.ajhg.2010.08.018.
19	Identification of HESX1 mutations in Kallmann syndrome. Fertil Steril. 2013 Jun;99(7):1831-7. doi: 10.1016/j.fertnstert.2013.01.149. Epub 2013 Mar 1.
20	Prevalence and associated phenotypes of PLXNA1 variants in normosmic and anosmic idiopathic hypogonadotropic hypogonadism.Clin Genet. 2019 Feb;95(2):320-324. doi: 10.1111/cge.13482. Epub 2018 Dec 26.
21	Mutational analysis of the necdin gene in patients with congenital isolated hypogonadotropic hypogonadism.Eur J Endocrinol. 2011 Jul;165(1):145-50. doi: 10.1530/EJE-11-0199. Epub 2011 May 4.
22	Nasal embryonic LHRH factor (NELF) mutations in patients with normosmic hypogonadotropic hypogonadism and Kallmann syndrome.Fertil Steril. 2011 Apr;95(5):1613-20.e1-7. doi: 10.1016/j.fertnstert.2011.01.010. Epub 2011 Feb 15.
23	Prokineticins and their G protein-coupled receptors in health and disease.Prog Mol Biol Transl Sci. 2019;161:149-179. doi: 10.1016/bs.pmbts.2018.09.006. Epub 2018 Oct 24.
24	Deletion of the Homeodomain Protein Six6 From GnRH Neurons Decreases GnRH Gene Expression, Resulting in Infertility.Endocrinology. 2019 Sep 1;160(9):2151-2164. doi: 10.1210/en.2019-00113.
25	Structure Based Substrate Specificity Analysis of Heparan Sulfate 6-O-Sulfotransferases.ACS Chem Biol. 2017 Jan 20;12(1):73-82. doi: 10.1021/acschembio.6b00841. Epub 2016 Nov 22.
26	Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism.Fertil Steril. 2018 Aug;110(3):486-495.e5. doi: 10.1016/j.fertnstert.2018.04.010.