Details of Disease

General Information of Disease (ID: DISYI2XZ)

• Disease Name: Precocious puberty
• Synonyms: idiopathic sexual precocity; familial precocious puberty; sexual precocity; pubertas praecox
• Definition: Unusually early sexual maturity.
• Disease Hierarchy:
  DIS4HEW4: Gonadal disorder
  DISQCXZX: Disorder of development or morphogenesis
  DISYI2XZ: Precocious puberty
• Disease Identifiers:
  MONDO ID: MONDO_0000088
  MESH ID: D011629
  UMLS CUI: C0034013
  MedGen ID: 18752
  HPO ID: HP:0000826
  Orphanet ID: 95708
  SNOMED CT ID: 400179000

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
FSHR	TTZFDBT	Limited	Genetic Variation	[1]
LHCGR	TT2O4W9	Limited	Genetic Variation	[2]
NR3C1	TTOZRK6	Limited	Genetic Variation	[3]
KCNT1	TTGJFK1	moderate	Genetic Variation	[4]
COASY	TT4YO0Z	Strong	Genetic Variation	[5]
CYP19A1	TTSZLWK	Strong	Biomarker	[6]
CYP21A2	TTP4GLG	Strong	Genetic Variation	[7]
GH1	TTT3YKH	Strong	Biomarker	[8]
GNRH1	TT0ID4A	Strong	Biomarker	[9]
IGF1	TTT6LOU	Strong	Biomarker	[10]
KISS1	TTU2O6T	Strong	Genetic Variation	[11]
KISS1R	TT3KBZY	Strong	Genetic Variation	[12]
NR0B1	TTTK36V	Strong	Genetic Variation	[13]
PROKR2	TTM67AX	Strong	Genetic Variation	[14]
CYP11B1	TTIQUX7	Definitive	Genetic Variation	[15]
ESRRG	TT9ZRHB	Definitive	Biomarker	[16]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CDKL5	OTGL5HRV	Limited	X-linked	[17]
CREBRF	OT2GK1HI	Limited	Biomarker	[18]
AMH	OT5FH4BD	Strong	Biomarker	[19]
LHB	OT5GBOVJ	Strong	Biomarker	[9]
LIN28B	OTVWP0FN	Strong	Genetic Variation	[20]
MKRN3	OTAFO4YR	Strong	Genetic Variation	[21]
POU1F1	OTXT8A5C	Strong	Genetic Variation	[22]
SMAD4	OTWQWCKG	Strong	Genetic Variation	[23]
C1QL1	OTNQ0G3E	Definitive	Biomarker	[24]
CUL9	OTPUCLZT	Definitive	Biomarker	[25]
IPP	OTCGBS3H	Definitive	Biomarker	[26]
PAPPA2	OTXYGTUZ	Definitive	Biomarker	[16]
TAC3	OTOJGM38	Definitive	Altered Expression	[10]

References

• [1] No activating mutations of FSH receptor in four children with ovarian juvenile granulosa cell tumors and the association of these tumors with central precocious puberty.J Pediatr Adolesc Gynecol. 2009 Jun;22(3):173-9. doi: 10.1016/j.jpag.2008.10.003.
• [2] Germ Cell Neoplasia in Situ and Preserved Fertility Despite Suppressed Gonadotropins in a Patient With Testotoxicosis.J Clin Endocrinol Metab. 2017 Dec 1;102(12):4411-4416. doi: 10.1210/jc.2017-01761.
• [3] An unexpected, mild phenotype of glucocorticoid resistance associated with glucocorticoid receptor gene mutation case report and review of the literature.BMC Med Genet. 2018 Mar 6;19(1):37. doi: 10.1186/s12881-018-0552-6.
• [4] KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP.Brain. 2019 Oct 1;142(10):2996-3008. doi: 10.1093/brain/awz240.
• [5] Detection of Rare Somatic GNAS Mutation in McCune-Albright Syndrome Using a Novel Peptide Nucleic Acid Probe in a Single Tube.Molecules. 2017 Nov 1;22(11):1874. doi: 10.3390/molecules22111874.
• [6] Is there a role for estrogen activity assays? Recombinant cell bioassay for estrogen: Development and applications.Steroids. 2015 Jul;99(Pt A):108-12. doi: 10.1016/j.steroids.2014.08.004. Epub 2014 Aug 24.
• [7] Unusual phenotype of congenital adrenal hyperplasia (CAH) with a novel mutation of the CYP21A2 gene.J Pediatr Endocrinol Metab. 2016 Jul 1;29(7):867-71. doi: 10.1515/jpem-2015-0457.
• [8] Contributing factors of mortality in Prader-Willi syndrome.Am J Med Genet A. 2019 Feb;179(2):196-205. doi: 10.1002/ajmg.a.60688. Epub 2018 Dec 19.
• [9] Update on the etiology, diagnosis and therapeutic management of sexual precocity.Arq Bras Endocrinol Metabol. 2008 Feb;52(1):18-31. doi: 10.1590/s0004-27302008000100005.
• [10] The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty.Gynecol Endocrinol. 2018 Jul;34(7):627-630. doi: 10.1080/09513590.2017.1423467. Epub 2018 Jan 5.
• [11] Kisspeptin/GPR54 System: What Do We Know About Its Role in Human Reproduction?.Cell Physiol Biochem. 2018;49(4):1259-1276. doi: 10.1159/000493406. Epub 2018 Sep 11.
• [12] Novel DNA variation of GPR54 gene in familial central precocious puberty.Ital J Pediatr. 2019 Jan 11;45(1):10. doi: 10.1186/s13052-019-0601-6.
• [13] Gonadotropin- and Adrenocorticotropic Hormone-Independent Precocious Puberty of Gonadal Origin in a Patient with Adrenal Hypoplasia Congenita Due to DAX1 Gene Mutation - A Case Report and Review of the Literature: Implications for the Pathomechanism.Horm Res Paediatr. 2019;91(5):336-345. doi: 10.1159/000495189. Epub 2018 Dec 11.
• [14] Paradoxical gain-of-function mutant of the G-protein-coupled receptor PROKR2 promotes early puberty.J Cell Mol Med. 2017 Oct;21(10):2623-2626. doi: 10.1111/jcmm.13146. Epub 2017 Mar 24.
• [15] Genetic aspects of congenital adrenal hyperplasia.J Pediatr Endocrinol Metab. 2001;14 Suppl 5:1303-8; discussion 1317.
• [16] Genomic association for sexual precocity in beef heifers using pre-selection of genes and haplotype reconstruction.PLoS One. 2018 Jan 2;13(1):e0190197. doi: 10.1371/journal.pone.0190197. eCollection 2018.
• [17] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [18] Pituitary gonadotropin-independent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis.J Pediatr. 1985 Jan;106(1):33-40. doi: 10.1016/s0022-3476(85)80460-1.
• [19] Androgens downregulate anti-Mllerian hormone promoter activity in the Sertoli cell through the androgen receptor and intact steroidogenic factor 1 sites.Biol Reprod. 2018 Dec 1;99(6):1303-1312. doi: 10.1093/biolre/ioy152.
• [20] Association between MKRN3 and LIN28B polymorphisms and precocious puberty.BMC Genet. 2018 Jul 27;19(1):47. doi: 10.1186/s12863-018-0658-z.
• [21] Investigation of MKRN3 Mutation in Patients with Familial Central Precocious Puberty.J Clin Res Pediatr Endocrinol. 2018 Jul 31;10(3):223-229. doi: 10.4274/jcrpe.5506. Epub 2018 Feb 28.
• [22] Precocious or early puberty in patients with combined pituitary hormone deficiency due to POU1F1 gene mutation: case report and review of possible mechanisms.Hormones (Athens). 2018 Dec;17(4):581-588. doi: 10.1007/s42000-018-0079-4. Epub 2018 Nov 20.
• [23] The first two Chinese Myhre syndrome patients with the recurrent SMAD4 pathogenic variants: Functional consequences and clinical diversity.Clin Chim Acta. 2020 Jan;500:128-134. doi: 10.1016/j.cca.2019.10.006. Epub 2019 Oct 22.
• [24] Overexpression of corticotropin releasing factor in the central nucleus of the amygdala advances puberty and disrupts reproductive cycles in female rats.Endocrinology. 2014 Oct;155(10):3934-44. doi: 10.1210/en.2014-1339. Epub 2014 Jul 22.
• [25] Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature.Horm Res. 1991;36(5-6):216-9. doi: 10.1159/000182166.
• [26] Improved final predicted height with the injection of leuprolide in children with earlier puberty: A retrospective cohort study.PLoS One. 2017 Oct 3;12(10):e0185080. doi: 10.1371/journal.pone.0185080. eCollection 2017.