KEGG DISEASE: 46,XY gonadal dysgenesis

DISEASE: 46,XY gonadal dysgenesis

Entry

H00607                      Disease

Name

46,XY gonadal dysgenesis

Subgroup

Campomelic dysplasia [DS:H00442]
Frasier syndrome (FS)
Denys-Drash syndrome (DDS)

Description

Gonadal dysgenesis (GD) is a disorder of sex development. Formerly, 46,XY GD was also known as 46,XY sex reversal (SRXY). In 46,XY GD, the gonadal histology can range from fibrous streak gonads to partial GD with presence of testicular tissue. The phenotype of patients with 46,XY GD can vary from normal female to genital ambiguity to an undervirilized male. Mutations involving the testis-determining gene SRY, and other genes involved in sex determination, such as the genes WT1, DHH, NR5A1, SOX9, FOG2/ZFPM2 and MAP3K1 have been identified.

Category

Reproductive system disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD2A  Malformative disorders of sex development
    H00607  46,XY gonadal dysgenesis
Pathway-based classification of diseases [BR:br08402]
Lipid/glycolipid metabolism
  nt06019  Steroid hormone biosynthesis
   H00607  46,XY gonadal dysgenesis

Pathway

hsa04927

Cortisol synthesis and secretion

hsa00140

Steroid hormone biosynthesis

Network

nt06019 Steroid hormone biosynthesis

Gene

(SRXY1) SRY [HSA:6736] [KO:K09266]
(SRXY2) NR0B1 [HSA:190] [KO:K08562]
(SRXY3) NR5A1 [HSA:2516] [KO:K08560]
(SRXY5) CBX2 [HSA:84733] [KO:K11451]
(SRXY6) MAP3K1 [HSA:4214] [KO:K04416]
(SRXY7) DHH [HSA:50846] [KO:K11990]
(SRXY8) AKR1C2 [HSA:1646] [KO:K00089]
(SRXY8) AKR1C4 [HSA:1109] [KO:K00037]
(SRXY9) ZFPM2 [HSA:23414] [KO:K17442]
(SRXY11) DHX37 [HSA:57647] [KO:K14780]
(FS/DDS) WT1 [HSA:7490] [KO:K09234]

Other DBs

ICD-11:

LD2A.1

ICD-10:

Q99.1

MeSH:

D006061

OMIM:

400044 300018 612965 613080 613762 233420 607080 614279 616067 273250 136680 194080

Reference

PMID:18279784

Authors

Hughes IA

Title

Disorders of sex development: a new definition and classification.

Journal

Best Pract Res Clin Endocrinol Metab 22:119-34 (2008)
DOI:10.1016/j.beem.2007.11.001

Reference

PMID:25813279

Authors

Bastian C, Muller JB, Lortat-Jacob S, Nihoul-Fekete C, Bignon-Topalovic J, McElreavey K, Bashamboo A, Brauner R

Title

Genetic mutations and somatic anomalies in association with 46,XY gonadal dysgenesis.

Journal

Fertil Steril 103:1297-304 (2015)
DOI:10.1016/j.fertnstert.2015.01.043

Reference

PMID:31745530 (SRXY1_2_7_11)

Authors

Buonocore F, Clifford-Mobley O, King TFJ, Striglioni N, Man E, Suntharalingham JP, Del Valle I, Lin L, Lagos CF, Rumsby G, Conway GS, Achermann JC

Title

Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD.

Journal

J Endocr Soc 3:2341-2360 (2019)
DOI:10.1210/js.2019-00306

Reference

PMID:17503084 (SRXY2)

Authors

Smyk M, Berg JS, Pursley A, Curtis FK, Fernandez BA, Bien-Willner GA, Lupski JR, Cheung SW, Stankiewicz P

Title

Male-to-female sex reversal associated with an approximately 250 kb deletion upstream of NR0B1 (DAX1).

Journal

Hum Genet 122:63-70 (2007)
DOI:10.1007/s00439-007-0373-8

Reference

PMID:23918653 (SRXY3)

Authors

Harrison SM, Campbell IM, Keays M, Granberg CF, Villanueva C, Tannin G, Zinn AR, Castrillon DH, Shaw CA, Stankiewicz P, Baker LA

Title

Screening and familial characterization of copy-number variations in NR5A1 in 46,XY disorders of sex development and premature ovarian failure.

Journal

Am J Med Genet A 161A:2487-94 (2013)
DOI:10.1002/ajmg.a.36084

Reference

PMID:19361780 (SRXY5)

Authors

Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ

Title

Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene.

Journal

Am J Hum Genet 84:658-63 (2009)
DOI:10.1016/j.ajhg.2009.03.016

Reference

PMID:21129722 (SRXY6)

Authors

Pearlman A, Loke J, Le Caignec C, White S, Chin L, Friedman A, Warr N, Willan J, Brauer D, Farmer C, Brooks E, Oddoux C, Riley B, Shajahan S, Camerino G, Homfray T, Crosby AH, Couper J, David A, Greenfield A, Sinclair A, Ostrer H

Title

Mutations in MAP3K1 cause 46,XY disorders of sex development and implicate a common signal transduction pathway in human testis determination.

Journal

Am J Hum Genet 87:898-904 (2010)
DOI:10.1016/j.ajhg.2010.11.003

Reference

PMID:21802064 (SRXY8)

Authors

Fluck CE, Meyer-Boni M, Pandey AV, Kempna P, Miller WL, Schoenle EJ, Biason-Lauber A

Title

Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation.

Journal

Am J Hum Genet 89:201-18 (2011)
DOI:10.1016/j.ajhg.2011.06.009

Reference

PMID:24549039 (SRXY9)

Authors

Bashamboo A, Brauner R, Bignon-Topalovic J, Lortat-Jacob S, Karageorgou V, Lourenco D, Guffanti A, McElreavey K

Title

Mutations in the FOG2/ZFPM2 gene are associated with anomalies of human testis determination.

Journal

Hum Mol Genet 23:3657-65 (2014)
DOI:10.1093/hmg/ddu074

Reference

PMID:9398852 (FS)

Authors

Barbaux S, Niaudet P, Gubler MC, Grunfeld JP, Jaubert F, Kuttenn F, Fekete CN, Souleyreau-Therville N, Thibaud E, Fellous M, McElreavey K

Title

Donor splice-site mutations in WT1 are responsible for Frasier syndrome.

Journal

Nat Genet 17:467-70 (1997)
DOI:10.1038/ng1297-467

Reference

PMID:18203154 (DDS)

Authors

Antonius T, van Bon B, Eggink A, van der Burgt I, Noordam K, van Heijst A

Title

Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097GA(Arg366His) mutation.

Journal

Am J Med Genet A 146A:496-9 (2008)
DOI:10.1002/ajmg.a.32168

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Disease (12)   
   OMIM (12)   
Gene (22)   
   KEGG ORTHOLOGY (11)   
   KEGG GENES (11)   
Literature (11)   
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