MCID: 46X052
MIFTS: 51

46,xx Sex Reversal 1

Categories: Genetic diseases, Rare diseases, Reproductive diseases, Endocrine diseases, Fetal diseases

Aliases & Classifications for 46,xx Sex Reversal 1

MalaCards integrated aliases for 46,xx Sex Reversal 1:

Name: 46,xx Sex Reversal 1 57 75
46,xx Testicular Disorder of Sex Development 57 53 25 59 75 29
46,xx Sex Reversal, Type 1 29 6 40
46,xx Gonadal Dysgenesis 53 59 6
46,xx Gonadal Dysgenesis, Complete, Sry-Positive 57 29
Ovotesticular Disorders of Sex Development 44 73
46,xx Testicular Dsd 53 59
True Hermaphroditism 59 29
46xx Sex Reversal 1 57 13
Xx Male Syndrome 53 25
Xx Sex Reversal 53 25
Srxx1 57 75
Follicular Stimulating Hormone-Resistant Ovaries 59
46,xx Ovotesticular Disorder of Sex Development 59
46,xx Gonadal Dysgenesis Complete Sry-Positive 75
46, Xx Testicular Disorders of Sex Development 73
Ovotesticular Disorder of Sex Development 75
46,xx True Hermaphroditism Sry-Positive 75
Hypergonadotropic Ovarian Dysgenesis 59
46,xx Complete Gonadal Dysgenesis 59
46,xx Sex Reversal, Sry-Positive 57
46,xx Sex Reversal Sry-Positive 75
46,xx Pure Gonadal Dysgenesis 59
Xx Female Gonadal Dysgenesis 59
46, Xx Gonadal Sex Reversal 53
46,xx Ovarian Dysgenesis 59
46,xx Ovotesticular Dsd 59
De La Chapelle Syndrome 59
Xx Male, Sry-Positive 57
Hermaphroditism, True 55
Xx Male Sry-Positive 75
46,xx Sex Reversal 25
Xx, Male Syndrome 59
Ovotesticular Dsd 75
Fsh-Ro 59
Xx-Gd 59

Characteristics:

Orphanet epidemiological data:

59
46,xx gonadal dysgenesis
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable,X-linked recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Adolescent,Adult; Age of death: normal life expectancy;
46,xx ovotesticular disorder of sex development
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;
46,xx testicular disorder of sex development
Prevalence: 1-9/100000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

HPO:

32
46,xx sex reversal 1:
Inheritance y-linked inheritance


Classifications:



Summaries for 46,xx Sex Reversal 1

NIH Rare Diseases : 53 46,XX testicular disorder of sex development is a condition in which a person with two X chromosomes (which is normally found in females) has a male appearance. More specifically, people with this condition have male external genitalia, ranging from normal to ambiguous. Other common signs and symptoms include small testes, gynecomastia, infertility due to azoospermia (lack of sperm), and health problems related to low testosterone. Less often, affected people may experience abnormalities such as undescended testes and hypospadias. Gender role and gender identity are normally reported as male. This condition may occur if the SRY gene (which is usually found on the Y chromosome) is misplaced onto the X chromosome. This generally occurs to do an abnormal exchange of genetic material between chromosomes (a translocation). Less commonly, the condition may be due to copy number variants or rearrangements in or around the SOX9 or SOX3 gene. In some affected people, the underlying cause is unknown. In most cases, the condition occurs sporadically in people with no family history of the condition. Treatment is based on the signs and symptoms present in each person and generally includes testosterone replacement therapy.

MalaCards based summary : 46,xx Sex Reversal 1, also known as 46,xx testicular disorder of sex development, is related to premature ovarian failure 1 and hermaphroditism. An important gene associated with 46,xx Sex Reversal 1 is SRY (Sex Determining Region Y), and among its related pathways/superpathways are Regulation of Androgen receptor activity and Ovarian steroidogenesis. Affiliated tissues include testes, ovary and uterus, and related phenotypes are gonadal dysgenesis and premature ovarian insufficiency

Genetics Home Reference : 25 46,XX testicular disorder of sex development is a condition in which individuals with two X chromosomes in each cell, the pattern normally found in females, have a male appearance. People with this disorder have male external genitalia. They generally have small testes and may also have abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Affected children are typically raised as males and have a male gender identity.

OMIM : 57 A disorder of sex development (DSD) is a 'congenital condition in which development of chromosomal, gonadal, or anatomic sex is atypical.' 46,XX DSD is a disorder of gonadal (ovarian) development, which may be complete or partial (Lee et al., 2006). 46,XX male sex reversal is a condition in which a phenotypically normal male has a female genotype. A 'true hermaphrodite' must have both mature ovarian and mature testicular tissue with histologic evidence of follicles and tubules, respectively (van Niekerk and Retief, 1981). It is a genetically heterogeneous condition. (400045)

UniProtKB/Swiss-Prot : 75 46,XX sex reversal 1: A condition in which male gonads develop in a genetic female (female to male sex reversal).

Wikipedia : 76 XX male syndrome is a rare congenital condition where an individual with a female genotype has... more...

Related Diseases for 46,xx Sex Reversal 1

Diseases related to 46,xx Sex Reversal 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 premature ovarian failure 1 31.0 BMP15 FSHR NR5A1
2 hermaphroditism 30.4 SOX9 SRY
3 46 xy gonadal dysgenesis 28.0 NR0B1 NR5A1 SOX3 SOX9 SRY
4 gonadal dysgenesis 26.3 BMP15 FSHR NR0B1 NR5A1 PSMC3IP SOX9
5 46,xx sex reversal 2 12.6
6 nonsyndromic 46,xx testicular disorders of sex development 12.4
7 46,xy ovotesticular disorder of sex development 12.4
8 46,xx gonadal dysgenesis epibulbar dermoid 12.2
9 46,xy sex reversal 1 11.6
10 palmoplantar hyperkeratosis with squamous cell carcinoma of skin and 46,xx sex reversal 11.4
11 ovarian dysgenesis 1 11.3
12 46,xx sex reversal 4 11.3
13 ovarian dysgenesis 4 11.2
14 ovarian dysgenesis 2 11.2
15 mixed gonadal dysgenesis 10.5 SOX9 SRY
16 anorchia 10.5 NR5A1 SRY
17 testicular disease 10.5 SOX9 SRY
18 gonadoblastoma 10.4 SOX9 SRY
19 campomelic dysplasia 10.4 SOX9 SRY
20 freemartinism 10.3 BMP15 SRY
21 androgen insensitivity syndrome 10.3 NR5A1 SRY
22 uterine hypoplasia 10.3 BMP15 PSMC3IP
23 frasier syndrome 10.1 NR5A1 SOX9 SRY
24 mayer-rokitansky-kuster-hauser syndrome 10.0
25 metabolic acidosis 10.0
26 pseudohermaphroditism 10.0 NR5A1 SRY
27 simpson-golabi-behmel syndrome 10.0
28 male reproductive system disease 9.9 FSHR SRY
29 squamous cell carcinoma 9.8
30 palmoplantar keratosis 9.8
31 adrenal cortical hypofunction 9.8 NR0B1 NR5A1
32 adrenal hypoplasia, congenital 9.7 NR0B1 NR5A1
33 anovulation 9.7 BMP15 FSHR
34 alternating hemiplegia of childhood 9.6 NR0B1 NR5A1 SRY
35 persistent mullerian duct syndrome 9.6 BMP15 NR5A1 SOX9 SRY
36 hypospadias 9.5 NR5A1 SOX9 SRD5A1 SRY
37 female reproductive system disease 9.5 BMP15 FSHR NR5A1
38 ovarian disease 9.5 BMP15 FSHR NR5A1
39 wilms tumor 1 9.5 NR0B1 NR5A1 SRY
40 amenorrhea 9.2 BMP15 FSHR NR5A1 SRY
41 reproductive system disease 9.2 BMP15 FSHR NR5A1 SRY
42 46,xy partial gonadal dysgenesis 9.2 NR0B1 NR5A1 SOX9 SRY
43 adrenal carcinoma 9.1 NR0B1 NR5A1
44 gonadal disease 8.9 FSHR NR0B1 NR5A1 SRY

Graphical network of the top 20 diseases related to 46,xx Sex Reversal 1:



Diseases related to 46,xx Sex Reversal 1

Symptoms & Phenotypes for 46,xx Sex Reversal 1

Clinical features from OMIM:

400045

Human phenotypes related to 46,xx Sex Reversal 1:

59 32 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gonadal dysgenesis 59 32 obligate (100%) Obligate (100%) HP:0000133
2 premature ovarian insufficiency 59 32 obligate (100%) Obligate (100%) HP:0008209
3 decreased fertility 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000144
4 primary amenorrhea 59 32 hallmark (90%) Very frequent (99-80%) HP:0000786
5 delayed puberty 59 32 hallmark (90%) Very frequent (99-80%) HP:0000823
6 increased circulating gonadotropin level 59 32 hallmark (90%) Very frequent (99-80%) HP:0000837
7 decreased serum estradiol 59 32 hallmark (90%) Very frequent (99-80%) HP:0008214
8 osteopenia 59 32 frequent (33%) Frequent (79-30%) HP:0000938
9 sparse pubic hair 59 32 frequent (33%) Frequent (79-30%) HP:0002225
10 delayed skeletal maturation 59 32 frequent (33%) Frequent (79-30%) HP:0002750
11 osteoporosis of vertebrae 59 32 frequent (33%) Frequent (79-30%) HP:0005625
12 aplasia/hypoplasia of the uterus 59 32 frequent (33%) Frequent (79-30%) HP:0008684
13 aplasia/hypoplasia of the breasts 59 32 frequent (33%) Frequent (79-30%) HP:0010311
14 streak ovary 59 32 frequent (33%) Frequent (79-30%) HP:0010464
15 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
16 secondary amenorrhea 59 32 occasional (7.5%) Occasional (29-5%) HP:0000869
17 abnormality of metabolism/homeostasis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001939
18 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
19 microcephaly 59 32 very rare (1%) Very rare (<4-1%) HP:0000252
20 arachnodactyly 59 32 very rare (1%) Very rare (<4-1%) HP:0001166
21 ataxia 59 32 very rare (1%) Very rare (<4-1%) HP:0001251
22 pulmonary fibrosis 59 32 very rare (1%) Very rare (<4-1%) HP:0002206
23 ambiguous genitalia 59 32 hallmark (90%) Excluded (0%),Very frequent (99-80%),Very frequent (99-80%) HP:0000062
24 abnormality of male internal genitalia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000022
25 cryptorchidism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000028
26 scrotal hypoplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000046
27 hypospadias 59 32 hallmark (90%) Very frequent (99-80%) HP:0000047
28 bifid scrotum 59 32 hallmark (90%) Very frequent (99-80%) HP:0000048
29 abnormality of the uterus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000130
30 polycystic ovaries 59 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000147
31 hypoplasia of penis 59 32 hallmark (90%) Very frequent (99-80%) HP:0008736
32 true hermaphroditism 59 32 hallmark (90%) Very frequent (99-80%) HP:0010459
33 abnormal scrotal rugation 59 32 hallmark (90%) Very frequent (99-80%) HP:0012856
34 urogenital sinus anomaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0100779
35 male hypogonadism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000026
36 decreased testicular size 59 32 hallmark (90%) Very frequent (99-80%) HP:0008734
37 precocious menopause 59 Obligate (100%)
38 abnormality of secondary sexual hair 59 Very frequent (99-80%)
39 reduced bone mineral density 59 Frequent (79-30%)
40 abnormality of female internal genitalia 59 Very frequent (99-80%)
41 sex reversal 32 HP:0012245

MGI Mouse Phenotypes related to 46,xx Sex Reversal 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.56 SOX9 SRD5A1 BMP15 FSHR NR0B1 NR5A1
2 reproductive system MP:0005389 9.28 BMP15 FSHR NR0B1 NR5A1 NUP107 PSMC3IP

Drugs & Therapeutics for 46,xx Sex Reversal 1

Search Clinical Trials , NIH Clinical Center for 46,xx Sex Reversal 1

Cochrane evidence based reviews: ovotesticular disorders of sex development

Genetic Tests for 46,xx Sex Reversal 1

Genetic tests related to 46,xx Sex Reversal 1:

# Genetic test Affiliating Genes
1 46,xx Testicular Disorder of Sex Development 29
2 46,xx Sex Reversal, Type 1 29 SRY
3 46,xx Gonadal Dysgenesis, Complete, Sry-Positive 29
4 True Hermaphroditism 29

Anatomical Context for 46,xx Sex Reversal 1

MalaCards organs/tissues related to 46,xx Sex Reversal 1:

41
Testes, Ovary, Uterus, Breast, Bone

Publications for 46,xx Sex Reversal 1

Articles related to 46,xx Sex Reversal 1:

# Title Authors Year
1
Ten cases with 46,XX testicular disorder of sex development: single center experience. ( 28379671 )
2017
2
Refining the regulatory region upstream of SOX9 associated with 46,XX testicular disorders of Sex Development (DSD). ( 25900885 )
2015
3
A duplication upstream of SOX9 was not positively correlated with the SRYa89negative 46,XX testicular disorder of sex development: A case report and literature review. ( 26260363 )
2015
4
A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication. ( 25077096 )
2014
5
Elucidation of distinctive genomic DNA structures in patients with 46,XX testicular disorders of sex development using genome wide analyses. ( 24576657 )
2014
6
Gene expression profile during testicular development in patients With SRY-negative 46,XX testicular disorder of sex development. ( 24149105 )
2013
7
Two males with SRY-positive 46,XX testicular disorder of sex development. ( 23110663 )
2013
8
De novo 12;17 translocation upstream of SOX9 resulting in 46,XX testicular disorder of sex development. ( 20082466 )
2010
9
46,XX Testicular Disorder of Sex Development ( 20301589 )
1993

Variations for 46,xx Sex Reversal 1

ClinVar genetic disease variations for 46,xx Sex Reversal 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 SRY NM_003140.2(SRY): c.331C> T (p.Gln111Ter) single nucleotide variant Pathogenic GRCh38 Chromosome Y, 2787273: 2787273
2 SRY NM_003140.2(SRY): c.331C> T (p.Gln111Ter) single nucleotide variant Pathogenic GRCh37 Chromosome Y, 2655314: 2655314
3 MRPS22 NM_020191.2(MRPS22): c.605G> A (p.Arg202His) single nucleotide variant Pathogenic rs753345594 GRCh37 Chromosome 3, 139069121: 139069121
4 MRPS22 NM_020191.2(MRPS22): c.605G> A (p.Arg202His) single nucleotide variant Pathogenic rs753345594 GRCh38 Chromosome 3, 139350279: 139350279

Expression for 46,xx Sex Reversal 1

Search GEO for disease gene expression data for 46,xx Sex Reversal 1.

Pathways for 46,xx Sex Reversal 1

Pathways related to 46,xx Sex Reversal 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.96 NR0B1 SRY
2 10.85 BMP15 FSHR
3 10.46 FSHR NR5A1
4 10.43 SOX3 SOX9 SRY

GO Terms for 46,xx Sex Reversal 1

Cellular components related to 46,xx Sex Reversal 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleoplasm GO:0005654 9.17 NR0B1 NR5A1 PSMC3IP SOX3 SOX9 SPIDR

Biological processes related to 46,xx Sex Reversal 1 according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 cell differentiation GO:0030154 9.92 NR0B1 NR5A1 SOX9 SRD5A1 SRY
2 positive regulation of transcription, DNA-templated GO:0045893 9.86 BMP15 NR5A1 SOX9 SRY
3 transcription initiation from RNA polymerase II promoter GO:0006367 9.71 NR0B1 NR5A1 SOX9
4 intracellular receptor signaling pathway GO:0030522 9.58 NR0B1 NR5A1
5 pituitary gland development GO:0021983 9.58 NR0B1 SOX3 SRD5A1
6 hormone-mediated signaling pathway GO:0009755 9.57 FSHR NR5A1
7 sex differentiation GO:0007548 9.55 SRD5A1 SRY
8 female gonad development GO:0008585 9.54 FSHR NR5A1 NUP107
9 female gamete generation GO:0007292 9.51 BMP15 FSHR
10 hypothalamus development GO:0021854 9.5 NR0B1 SOX3 SRD5A1
11 adrenal gland development GO:0030325 9.49 NR0B1 NR5A1
12 gonad development GO:0008406 9.48 FSHR NR0B1
13 Sertoli cell development GO:0060009 9.46 FSHR SOX9
14 Sertoli cell differentiation GO:0060008 9.43 NR0B1 SOX9
15 male sex determination GO:0030238 9.43 NR0B1 SOX9 SRY
16 male gonad development GO:0008584 9.35 FSHR NR0B1 NR5A1 SOX9 SRD5A1
17 positive regulation of male gonad development GO:2000020 9.33 NR5A1 SOX9 SRY
18 sex determination GO:0007530 8.92 NR0B1 NR5A1 SOX3 SRD5A1

Molecular functions related to 46,xx Sex Reversal 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.63 NR0B1 NR5A1 PSMC3IP SOX3 SOX9 SRY
2 steroid hormone receptor activity GO:0003707 9.26 NR0B1 NR5A1
3 nuclear receptor activity GO:0004879 8.96 NR0B1 NR5A1
4 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 8.8 NR5A1 SOX9 SRY

Sources for 46,xx Sex Reversal 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MedGen
44 MeSH
45 MESH via Orphanet
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49 NCI
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51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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