Details of Disease

General Information of Disease (ID: DISRMAEZ)

• Disease Name: Disorder of sexual differentiation
• Synonyms: disorders of sex development (DSD); DSD; CARD; sexual differentiation disorder; sex differentiation disorder; sex differentiation disease; intersex conditions; intersex; disorders of sex development; disorder of sexual differentiation; disorder of sex differentiation; disorder of sex development; differences of sex development; conditions affecting reproductive development
• Definition: A congenital disorder characterized by abnormalities in the development of the sexual characteristics.
• Disease Hierarchy:
  DISWD40R: Disease
  DIS4HEW4: Gonadal disorder
  DIS7GG31: Developmental defect during embryogenesis
  DISRMAEZ: Disorder of sexual differentiation
• Disease Identifiers:
  MONDO ID: MONDO_0002145
  MESH ID: D012734
  UMLS CUI: C2930619
  MedGen ID: 415936
  Orphanet ID: 90771
  SNOMED CT ID: 39179006

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AKR1C3	TT5ZWB6	Limited	Biomarker	[1]
LHCGR	TT2O4W9	Limited	Biomarker	[2]
GART	TTEXB9Z	moderate	Genetic Variation	[3]
AADAT	TTT3IXG	Strong	Biomarker	[4]
BRIP1	TTZV7LJ	Strong	Genetic Variation	[5]
HHAT	TT1VNCG	Strong	Genetic Variation	[6]
HSD17B13	TTDJYZR	Strong	Genetic Variation	[7]
MAP3K1	TTW8TJI	Strong	Genetic Variation	[8]
NR0B1	TTTK36V	Strong	Biomarker	[9]
RNMT	TTG45HY	Strong	Genetic Variation	[10]
RSPO1	TTI9HL4	Strong	Biomarker	[11]
SLC22A3	TTG2UMS	Strong	Altered Expression	[12]
SRD5A2	TTT02K8	Strong	Genetic Variation	[13]
STAR	TTEI40H	Strong	Biomarker	[14]

This Disease Is Related to 4 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
AKR1C1	DE7P2FB	Limited	Biomarker	[1]
AKR1C2	DEOY5ZM	Limited	Biomarker	[1]
HSD17B3	DEX8J7E	Disputed	Genetic Variation	[15]
HSD17B7	DEDMWFX	Strong	Genetic Variation	[7]

This Disease Is Related to 29 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SOX10	OTF25ULQ	Limited	Biomarker	[16]
AMH	OT5FH4BD	Disputed	Altered Expression	[17]
PAICS	OTMZN747	moderate	Genetic Variation	[3]
SAMD9	OTDG48P0	moderate	Genetic Variation	[18]
BMPER	OTBYON4H	Strong	Genetic Variation	[19]
CDIPT	OTZX703K	Strong	Genetic Variation	[20]
CST9	OT37U1C8	Strong	Biomarker	[21]
CST9L	OT7GBIWW	Strong	Biomarker	[21]
DDX3Y	OTKL1FNX	Strong	Biomarker	[22]
DHRS11	OTU3J0ZL	Strong	Genetic Variation	[7]
EFCAB6	OT5G7GKB	Strong	Genetic Variation	[5]
EMX2	OT0V8OYK	Strong	Genetic Variation	[23]
FOXF2	OTV20NGX	Strong	Genetic Variation	[24]
FOXL2	OTFRQUYL	Strong	Altered Expression	[25]
GADD45G	OT8V1J4M	Strong	Biomarker	[26]
GDAP1	OTQE1O25	Strong	Genetic Variation	[27]
GSDMD	OTH39BKI	Strong	Biomarker	[28]
MAVS	OTTQ0J64	Strong	Genetic Variation	[29]
MEOX1	OTJEMT2D	Strong	Biomarker	[30]
MPZ	OTAR2YXH	Strong	Genetic Variation	[10]
NLRP6	OTEREN4W	Strong	Altered Expression	[31]
NR5A1	OTOULYR4	Strong	Genetic Variation	[32]
PAX1	OT0Y3MIM	Strong	Biomarker	[30]
PMP22	OTXWYWCZ	Strong	Genetic Variation	[10]
SOX3	OT1CRCOB	Strong	Biomarker	[33]
STARD8	OTY9IAKW	Strong	Biomarker	[34]
TINAGL1	OTZZO56M	Strong	Biomarker	[35]
TSPY1	OTPY57X4	Strong	Biomarker	[22]
TSPY3	OTQK3AKI	Strong	Biomarker	[22]

References

• [1] The aldo-keto reductases (AKRs): Overview.Chem Biol Interact. 2015 Jun 5;234:236-46. doi: 10.1016/j.cbi.2014.09.024. Epub 2014 Oct 7.
• [2] Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis, perturbation of which leads to masculinization disorders in rodents.PLoS One. 2012;7(5):e37064. doi: 10.1371/journal.pone.0037064. Epub 2012 May 17.
• [3] A novel mutation (c.T3816 > C) in the androgen receptor gene in a 46,XY female patient with androgen insensitivity syndrome.Endokrynol Pol. 2013;64(5):398-402. doi: 10.5603/EP.2013.0023.
• [4] Effect of urethral wall injection of replication-defective herpes simplex virus-mediated gene transfer of kynurenine aminotransferase on urethral pressure in spinal cord-injured rats.Neurourol Urodyn. 2017 Apr;36(4):1046-1051. doi: 10.1002/nau.23067. Epub 2016 Jul 8.
• [5] Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.Mol Genet Genomic Med. 2019 Jul;7(7):e00694. doi: 10.1002/mgg3.694. Epub 2019 May 23.
• [6] Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. PLoS Genet. 2014 May 1;10(5):e1004340. doi: 10.1371/journal.pgen.1004340. eCollection 2014 May.
• [7] A novel missense mutation in HSD17B3 gene in a 46, XY adolescent presenting with primary amenorrhea and virilization at puberty.Clin Chim Acta. 2015 Jan 1;438:154-6. doi: 10.1016/j.cca.2014.07.025. Epub 2014 Jul 24.
• [8] Mutations in MAP3K1 that cause 46,XY disorders of sex development disrupt distinct structural domains in the protein.Hum Mol Genet. 2019 May 15;28(10):1620-1628. doi: 10.1093/hmg/ddz002.
• [9] Disorders of sex development: Genetic characterization of a patient cohort.Mol Med Rep. 2020 Jan;21(1):97-106. doi: 10.3892/mmr.2019.10819. Epub 2019 Nov 12.
• [10] Molecular basis of hereditary neuropathies.Phys Med Rehabil Clin N Am. 2001 May;12(2):277-91.
• [11] Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with palmoplantar keratoderma: A review of literature and expansion of clinical phenotype.Am J Med Genet A. 2018 Apr;176(4):1006-1010. doi: 10.1002/ajmg.a.38646.
• [12] Is a CIS phenotype apparent in children with Disorders of Sex Development? Milder testicular dysgenesis is associated with a higher risk of malignancy.Andrology. 2015 Jan;3(1):59-69. doi: 10.1111/andr.301. Epub 2015 Jan 19.
• [13] 5-Reductase type 2 deficiency in families from an isolated Andean population in Venezuela.Ann Hum Genet. 2020 Mar;84(2):151-160. doi: 10.1111/ahg.12358. Epub 2019 Oct 15.
• [14] Presence of Germ Cells in Disorders of Sex Development: Implications for Fertility Potential and Preservation.J Urol. 2017 Mar;197(3 Pt 2):937-943. doi: 10.1016/j.juro.2016.08.108. Epub 2016 Nov 10.
• [15] 46,XY disorder of sex development (DSD) due to 17-hydroxysteroid dehydrogenase type 3 deficiency.J Steroid Biochem Mol Biol. 2017 Jan;165(Pt A):79-85. doi: 10.1016/j.jsbmb.2016.05.002. Epub 2016 May 6.
• [16] 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.Am J Med Genet A. 2017 Apr;173(4):1066-1070. doi: 10.1002/ajmg.a.38109.
• [17] Regulation of anti-Mllerian hormone (AMH) in males and the associations of serum AMH with the disorders of male fertility.Asian J Androl. 2019 Mar-Apr;21(2):109-114. doi: 10.4103/aja.aja_83_18.
• [18] MIRAGE syndrome is a rare cause of 46,XY DSD born SGA without adrenal insufficiency.PLoS One. 2018 Nov 7;13(11):e0206184. doi: 10.1371/journal.pone.0206184. eCollection 2018.
• [19] Diaphanospondylodysostosis: Refining the prenatal diagnosis of a rare skeletal disorder.Eur J Med Genet. 2019 Mar;62(3):167-171. doi: 10.1016/j.ejmg.2018.07.004. Epub 2018 Jul 10.
• [20] Ovarian-specific expression of a new gene regulated by the goat PIS region and transcribed by a FOXL2 bidirectional promoter.Genomics. 2005 Jun;85(6):715-26. doi: 10.1016/j.ygeno.2005.02.011.
• [21] Isolation of the human testatin gene and analysis in patients with abnormal gonadal development.Mol Hum Reprod. 2002 Jan;8(1):8-15. doi: 10.1093/molehr/8.1.8.
• [22] Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY.Hum Reprod. 2019 Apr 1;34(4):770-779. doi: 10.1093/humrep/dez004.
• [23] Severe sex differentiation disorder in a boy with a 3.8 Mb 10q25.3-q26.12 microdeletion encompassing EMX2.Am J Med Genet A. 2014 Oct;164A(10):2618-22. doi: 10.1002/ajmg.a.36662. Epub 2014 Jun 26.
• [24] Mutation analysis of FOXF2 in patients with disorders of sex development (DSD) in combination with cleft palate.Sex Dev. 2008;2(6):302-8. doi: 10.1159/000195679. Epub 2009 Mar 10.
• [25] Non-coding variation in disorders of sex development.Clin Genet. 2017 Feb;91(2):163-172. doi: 10.1111/cge.12911.
• [26] Gadd45g is essential for primary sex determination, male fertility and testis development.PLoS One. 2013;8(3):e58751. doi: 10.1371/journal.pone.0058751. Epub 2013 Mar 13.
• [27] Compound heterozygous deletions of PMP22 causing severe Charcot-Marie-Tooth disease of the Dejerine-Sottas disease phenotype. Am J Med Genet A. 2008 Sep 15;146A(18):2412-6. doi: 10.1002/ajmg.a.32456.
• [28] Exosomes Mediate Hippocampal and Cortical Neuronal Injury Induced by Hepatic Ischemia-Reperfusion Injury through Activating Pyroptosis in Rats.Oxid Med Cell Longev. 2019 Nov 13;2019:3753485. doi: 10.1155/2019/3753485. eCollection 2019.
• [29] The inflammasome in alcoholic hepatitis: Its relationship with Mallory-Denk body formation.Exp Mol Pathol. 2014 Oct;97(2):305-13. doi: 10.1016/j.yexmp.2014.08.006. Epub 2014 Aug 19.
• [30] Diaphanospondylodysostosis: six new cases and exclusion of the candidate genes, PAX1 and MEOX1.Am J Med Genet A. 2007 Oct 1;143A(19):2292-302. doi: 10.1002/ajmg.a.31934.
• [31] Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome.World J Gastroenterol. 2019 Aug 28;25(32):4696-4714. doi: 10.3748/wjg.v25.i32.4696.
• [32] NR5A1 gene variants repress the ovarian-specific WNT signaling pathway in 46,XX disorders of sex development patients.Hum Mutat. 2019 Feb;40(2):207-216. doi: 10.1002/humu.23672. Epub 2018 Nov 30.
• [33] Testis development in the absence of SRY: chromosomal rearrangements at SOX9 and SOX3.Eur J Hum Genet. 2015 Aug;23(8):1025-32. doi: 10.1038/ejhg.2014.237. Epub 2014 Nov 5.
• [34] A Case of Two Sisters Suffering from 46,XY Gonadal Dysgenesis and Carrying a Mutation of a Novel Candidate Sex-Determining Gene STARD8 on the X Chromosome.Sex Dev. 2018;12(4):191-195. doi: 10.1159/000489692. Epub 2018 Jun 8.
• [35] Luteolin alleviates NLRP3 inflammasome activation and directs macrophage polarization in lipopolysaccharide-stimulated RAW264.7 cells.Am J Transl Res. 2018 Jan 15;10(1):265-273. eCollection 2018.