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46,XY sex reversal 2(DSS; SRXY2)

MedGen UID:
341190
•Concept ID:
C1848296
•
Disease or Syndrome
Synonyms: 46,XY SEX REVERSAL, DAX1-RELATED; 46XY sex reversal 2, dosage-sensitive; Dosage-sensitive sex reversal; NR0B1-Related 46,XY CGD; NR0B1-related 46,XY complete gonadal dysgenesis
 
Gene (location): NR0B1 (Xp21.2)
 
Monarch Initiative: MONDO:0010226
OMIM®: 300018

Definition

Sex reversal in an individual with 46,XY karyotype caused by point mutations or deletions in the NR0B1 gene, encoding nuclear receptor subfamily 0 group B member 1. [from NCI]

Clinical features

From HPO
Sex reversal
MedGen UID:
868596
•Concept ID:
C4022995
•
Finding
Development of the reproductive system is inconsistent with the chromosomal sex.
See: Feature record | Search on this feature

Professional guidelines

PubMed

Primary amenorrhoea - cytogenetic study in 40 Indian women.
Banerjee B, Dutta A, Roy S, Halder A
J Obstet Gynaecol 2024 Dec;44(1):2348085. Epub 2024 May 6 doi: 10.1080/01443615.2024.2348085. PMID: 38708796
New insights into 5α-reductase type 2 deficiency based on a multi-centre study: regional distribution and genotype-phenotype profiling of SRD5A2 in 190 Chinese patients.
Gui B, Song Y, Su Z, Luo FH, Chen L, Wang X, Chen R, Yang Y, Wang J, Zhao X, Fan L, Liu X, Wang Y, Chen S, Gong C
J Med Genet 2019 Oct;56(10):685-692. Epub 2019 Jun 11 doi: 10.1136/jmedgenet-2018-105915. PMID: 31186340
Idiopathic male pseudohermaphroditism: variations in presentation and management.
Meau-Petit V, Marcou V, Trivin C, Lortat-Jacob S, McElreavey K, Brauner R
J Pediatr Endocrinol Metab 2005 Jun;18(6):569-75. doi: 10.1515/jpem.2005.18.6.569. PMID: 16042324

Recent clinical studies

Etiology

Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal Dysgenesis.
Rjiba K, Slimani W, Gaddas M, Hassine IH, Jelloul A, Khelifa HB, El Amri F, Zaouali M, Mcelreavey K, Saad A, Mougou-Zerelli S
J Clin Res Pediatr Endocrinol 2023 Feb 27;15(1):25-34. Epub 2022 Aug 19 doi: 10.4274/jcrpe.galenos.2022.2022-3-15. PMID: 35984215Free PMC Article
Aetiological bases of 46,XY disorders of sex development in the Hong Kong Chinese population.
Chan AO, But WM, Lee CY, Lam YY, Ng KL, Loung PY, Lam A, Cheng CW, Shek CC, Wong WS, Wong KF, Wong MY, Tse WY
Hong Kong Med J 2015 Dec;21(6):499-510. Epub 2015 Oct 16 doi: 10.12809/hkmj144402. PMID: 26492835
Identification of novel SRY mutations and SF1 (NR5A1) changes in patients with pure gonadal dysgenesis and 46,XY karyotype.
Paliwal P, Sharma A, Birla S, Kriplani A, Khadgawat R, Sharma A
Mol Hum Reprod 2011 Jun;17(6):372-8. Epub 2011 Jan 17 doi: 10.1093/molehr/gar002. PMID: 21242195
A study of gender outcome of Egyptian patients with 46,XY disorder of sex development.
Ismail SI, Mazen IA
Sex Dev 2010 Sep;4(4-5):285-91. Epub 2010 Jul 24 doi: 10.1159/000317120. PMID: 20664246
Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene.
Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ
Am J Hum Genet 2009 May;84(5):658-63. Epub 2009 Apr 9 doi: 10.1016/j.ajhg.2009.03.016. PMID: 19361780Free PMC Article

Diagnosis

FGF9 variant in 46,XY DSD patient suggests a role for dimerization in sex determination.
Croft B, Bird AD, Ono M, Eggers S, Bagheri-Fam S, Ryan JM, Reyes AP, van den Bergen J, Baxendale A, Thompson EM, Kueh AJ, Stanton P, Thomas T, Sinclair AH, Harley VR
Clin Genet 2023 Mar;103(3):277-287. Epub 2022 Nov 28 doi: 10.1111/cge.14261. PMID: 36349847Free PMC Article
Genetic analysis of a Taiwanese family identifies a DMRT3-OAS3 interaction that is involved in human sexual differentiation through the regulation of ESR1 expression.
Tsai CL, Tsai CN, Lee YS, Wang HS, Lee LY, Lin CY, Yang SY, Chao A
Fertil Steril 2020 Jul;114(1):133-143. Epub 2020 Jun 16 doi: 10.1016/j.fertnstert.2020.03.008. PMID: 32553473
FGFR2 mutation in 46,XY sex reversal with craniosynostosis.
Bagheri-Fam S, Ono M, Li L, Zhao L, Ryan J, Lai R, Katsura Y, Rossello FJ, Koopman P, Scherer G, Bartsch O, Eswarakumar JV, Harley VR
Hum Mol Genet 2015 Dec 1;24(23):6699-710. Epub 2015 Sep 11 doi: 10.1093/hmg/ddv374. PMID: 26362256Free PMC Article
Are human male patients with DAX1/NR0B1 mutations infertile?
Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Xp-duplications with and without sex reversal.
Baumstark A, Barbi G, Djalali M, Geerkens C, Mitulla B, Mattfeldt T, de Almeida JC, Vargas FR, Llerena Júnior JC, Vogel W, Just W
Hum Genet 1996 Jan;97(1):79-86. doi: 10.1007/BF00218838. PMID: 8557267

Therapy

Are human male patients with DAX1/NR0B1 mutations infertile?
Ravel C, Hyon C, Siffroi JP, Christin-Maitre S
Ann Endocrinol (Paris) 2014 May;75(2):126-7. Epub 2014 Apr 21 doi: 10.1016/j.ando.2014.03.003. PMID: 24751136
Spurious case of XX maleness in a patient with a history of Wiskott-Aldrich syndrome.
Nebesio TD, Torres-Martinez W, Rink RC, Eugster EA
Endocr Pract 2011 Mar-Apr;17(2):e1-3. doi: 10.4158/EP10242.CR. PMID: 21041165
Gender identity reversal in an adolescent with mixed gonadal dysgenesis.
Birnbacher R, Marberger M, Weissenbacher G, Schober E, Frisch H
J Pediatr Endocrinol Metab 1999 Sep-Oct;12(5):687-90. doi: 10.1515/jpem.1999.12.5.687. PMID: 10703543
Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood.
Bradley SJ, Oliver GD, Chernick AB, Zucker KJ
Pediatrics 1998 Jul;102(1):e9. doi: 10.1542/peds.102.1.e9. PMID: 9651461

Prognosis

Deafness DFNB128 Associated with a Recessive Variant of Human MAP3K1 Recapitulates Hearing Loss of Map3k1-Deficient Mice.
Faridi R, Yousaf R, Inagaki S, Olszewski R, Gu S, Morell RJ, Wilson E, Xia Y, Qaiser TA, Rashid M, Fenollar-Ferrer C, Hoa M, Riazuddin S, Friedman TB
Genes (Basel) 2024 Jun 27;15(7) doi: 10.3390/genes15070845. PMID: 39062623Free PMC Article
The human doublesex-related gene, DMRT2, is homologous to a gene involved in somitogenesis and encodes a potential bicistronic transcript.
Ottolenghi C, Veitia R, Barbieri M, Fellous M, McElreavey K
Genomics 2000 Mar 1;64(2):179-86. doi: 10.1006/geno.2000.6120. PMID: 10729224
Experiment of nurture: ablatio penis at 2 months, sex reassignment at 7 months, and a psychosexual follow-up in young adulthood.
Bradley SJ, Oliver GD, Chernick AB, Zucker KJ
Pediatrics 1998 Jul;102(1):e9. doi: 10.1542/peds.102.1.e9. PMID: 9651461

Clinical prediction guides

Anomalies in Human Sex Determination: Usefulness of a Combined Cytogenetic Approach to Characterize an Additional Case with Xp Functional Disomy Associated with 46,XY Gonadal Dysgenesis.
Rjiba K, Slimani W, Gaddas M, Hassine IH, Jelloul A, Khelifa HB, El Amri F, Zaouali M, Mcelreavey K, Saad A, Mougou-Zerelli S
J Clin Res Pediatr Endocrinol 2023 Feb 27;15(1):25-34. Epub 2022 Aug 19 doi: 10.4274/jcrpe.galenos.2022.2022-3-15. PMID: 35984215Free PMC Article
Protection Against XY Gonadal Sex Reversal by a Variant Region on Mouse Chromosome 13.
Livermore C, Simon M, Reeves R, Stévant I, Nef S, Pope M, Mallon AM, Wells S, Warr N, Greenfield A
Genetics 2020 Feb;214(2):467-477. Epub 2019 Dec 13 doi: 10.1534/genetics.119.302786. PMID: 31836612Free PMC Article
Human Sex Determination at the Edge of Ambiguity: INHERITED XY SEX REVERSAL DUE TO ENHANCED UBIQUITINATION AND PROTEASOMAL DEGRADATION OF A MASTER TRANSCRIPTION FACTOR.
Racca JD, Chen YS, Yang Y, Phillips NB, Weiss MA
J Biol Chem 2016 Oct 14;291(42):22173-22195. Epub 2016 Aug 30 doi: 10.1074/jbc.M116.741959. PMID: 27576690Free PMC Article
A novel human sex-determining gene linked to Xp11.21-11.23.
Rajender S, Thangaraj K, Gupta NJ, Leelavathy N, Rani DS, Nambiar RG, Kalavathy V, Santhiya ST, Rajangam S, Gopinath PM, Chakravarty B, Singh L
J Clin Endocrinol Metab 2006 Oct;91(10):4028-36. Epub 2006 Jul 25 doi: 10.1210/jc.2006-0950. PMID: 16868052
Genetic study of SOX9 in a case of campomelic dysplasia.
Giordano J, Prior HM, Bamforth JS, Walter MA
Am J Med Genet 2001 Jan 15;98(2):176-81. doi: 10.1002/1096-8628(20010115)98:2<176::aid-ajmg1027>3.0.co;2-q. PMID: 11223854

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