MCID: PRS049
MIFTS: 49

Persistent Mullerian Duct Syndrome

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

Aliases & Classifications for Persistent Mullerian Duct Syndrome

MalaCards integrated aliases for Persistent Mullerian Duct Syndrome:

Name: Persistent Mullerian Duct Syndrome 12 53 29 6 44 15 25
Persistent Oviduct Syndrome 53 25
Pmds 53 25
Mullerian Duct Syndrome. Persistent, Types I and Ii 40
Persistent Mullerian Duct Syndrome, Types 1 and 2 53
Female Genital Ducts in Otherwise Normal Male 53
Persistent Muellerian Duct Syndrome 12
Hernia Uteri Inguinale 53

Classifications:



External Ids:

Disease Ontology 12 DOID:0050791
MeSH 44 C536665
NCIt 50 C120188
SNOMED-CT 68 702358005
SNOMED-CT via HPO 69 396232000 204878001 111332007
UMLS 73 C1849930

Summaries for Persistent Mullerian Duct Syndrome

NIH Rare Diseases : 53 Persistent Mullerian duct syndrome (PMDS) is a disorder of sexual development that affects males. Males with PMDS have normal male reproductive organs and normal male external genitalia. However, they also have a uterus and fallopian tubes (female reproductive organs). The uterus and fallopian tubes develop from a structure called the Müllerian duct, which is present in both male and female fetuses. It typically breaks down in males, but it remains in those with PMDS. Early signs of PMDS may include undescended testes (cryptorchidism) or inguinal hernias. The uterus and fallopian tubes are often incidentally noticed during surgery to treat these conditions. Other features of PMDS may include abnormal positioning of the testes and female reproductive organs; transverse testicular ectopia (when both testicles descend on the same side); and infertility. PMDS is caused by mutations in the AMH gene (PMDS type 1) or AMHR2 gene (PMDS type 2). It is inherited in an autosomal recessive manner. In some cases, the genetic cause is unknown. Treatment may involve surgery to place the testes within the scrotum and remove Müllerian structures. If not treated, undescended testes may degenerate or develop cancer.

MalaCards based summary : Persistent Mullerian Duct Syndrome, also known as persistent oviduct syndrome, is related to persistent mullerian duct syndrome, types i and ii and pseudohermaphroditism. An important gene associated with Persistent Mullerian Duct Syndrome is AMH (Anti-Mullerian Hormone), and among its related pathways/superpathways are PAK Pathway and Gastric cancer. Affiliated tissues include uterus, testes and cervix, and related phenotypes are inguinal hernia and cryptorchidism

Disease Ontology : 12 A pseudohermaphroditism that is characterized by the persistence of Mullerian duct derivatives (i.e. uterus, cervix, fallopian tubes and upper two thirds of vagina) in a phenotypically and karyotypically male.

Related Diseases for Persistent Mullerian Duct Syndrome

Diseases in the Persistent Mullerian Duct Syndrome family:

Persistent Mullerian Duct Syndrome, Types I and Ii

Diseases related to Persistent Mullerian Duct Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 persistent mullerian duct syndrome, types i and ii 35.0 AMH AMHR2
2 pseudohermaphroditism 29.9 AMH AMHR2 NR5A1 SRY WT1
3 hypospadias 27.5 FGFR2 INSL3 NR5A1 SOX9 SRY WT1
4 pelizaeus-merzbacher disease 12.1
5 spastic paraplegia 2, x-linked 11.1
6 microphthalmia, syndromic 9 11.1
7 pelizaeus-merzbacher-like disease 11.1
8 sex differentiation disease 10.6 AMH AMHR2 SRY
9 freemartinism 10.5 AMH BMP15 SRY
10 gonadal disease 10.4 AMH NR5A1 SRY
11 anorchia 10.4 INSL3 NR5A1 SRY
12 female reproductive system disease 10.4 AMH BMP15 NR5A1
13 amenorrhea 10.3 BMP15 NR5A1 SRY
14 seminoma 10.3
15 inguinal hernia 10.3
16 reproductive system disease 10.2 AMH BMP15 NR5A1 SRY
17 ovarian disease 10.2 AMH BMP15 NR5A1
18 physical disorder 10.1 AMH BMP4 INSL3
19 testicular disease 10.1 INSL3 SOX9 SRY
20 testicular gonadoblastoma 10.0 KIT WT1
21 testicular seminoma 10.0
22 premature ovarian failure 1 10.0 AMH BMP15 NR5A1 WT1
23 mixed gonadal dysgenesis 10.0 AMH AMHR2 SOX9 SRY
24 female reproductive endometrioid cancer 10.0 CTNNB1 WT1
25 premature centromere division 9.9
26 hypogonadotropic hypogonadism 9.9
27 endometriosis of ovary 9.9
28 endometriosis 9.9
29 teratoma 9.9
30 hydrocele 9.9
31 type i 9.9
32 46,xx sex reversal 1 9.9 BMP15 NR5A1 SOX9 SRY
33 humeroradial synostosis 9.9 FGFR2 WNT7A
34 46,xy partial gonadal dysgenesis 9.8 NR5A1 SOX9 SRY WT1
35 46 xy gonadal dysgenesis 9.7 NR5A1 SOX9 SRY WT1
36 chromosome 10q26 deletion syndrome 9.7 AMH FGFR2 NOTCH2
37 wilms tumor 1 9.7 CTNNB1 NR5A1 SRY WT1
38 cryptorchidism, unilateral or bilateral 9.6 AMH AMHR2 INSL3 NR5A1 SRY WT1
39 desmoid tumor 9.5 CTNNB1 KIT
40 frasier syndrome 9.5 AMH NR5A1 SOX9 SRY WT1
41 conventional fibrosarcoma 9.3 CTNNB1 KIT
42 dysgerminoma of ovary 9.1 FGFR2 KIT WT1
43 gonadoblastoma 9.0 KIT SOX9 SRY TSPY1 WT1
44 gonadal dysgenesis 8.9 AMH BMP15 NR5A1 SOX9 SRY TSPY1
45 uterine carcinosarcoma 8.8 CTNNB1 FGFR2 KIT

Graphical network of the top 20 diseases related to Persistent Mullerian Duct Syndrome:



Diseases related to Persistent Mullerian Duct Syndrome

Symptoms & Phenotypes for Persistent Mullerian Duct Syndrome

Human phenotypes related to Persistent Mullerian Duct Syndrome:

32
# Description HPO Frequency HPO Source Accession
1 inguinal hernia 32 frequent (33%) HP:0000023
2 cryptorchidism 32 hallmark (90%) HP:0000028
3 male pseudohermaphroditism 32 frequent (33%) HP:0000037

MGI Mouse Phenotypes related to Persistent Mullerian Duct Syndrome:

46 (show all 20)
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.39 WT1 WNT7A AMH AMHR2 BMP5 BMP15
2 cardiovascular system MP:0005385 10.37 WNT7A WT1 AMHR2 BMP5 BMP4 CTNNB1
3 embryo MP:0005380 10.34 WNT7A WT1 AMHR2 BMP5 BMP4 CTNNB1
4 cellular MP:0005384 10.28 WT1 SOX9 BMP4 AMHR2 FGFR2 CTNNB1
5 growth/size/body region MP:0005378 10.28 WT1 BMP4 AMHR2 BMP5 FGFR2 CTNNB1
6 mortality/aging MP:0010768 10.23 WNT7A WT1 BMP4 AMHR2 BMP5 FGFR2
7 digestive/alimentary MP:0005381 10.17 BMP4 BMP5 CTNNB1 FURIN FGFR2 KIT
8 integument MP:0010771 10.16 WNT7A BMP4 AMHR2 CTNNB1 FURIN FGFR2
9 limbs/digits/tail MP:0005371 10.15 WNT7A BMP5 BMP4 CTNNB1 FURIN FGFR2
10 craniofacial MP:0005382 10.12 BMP4 BMP5 FGFR2 CTNNB1 KIT SOX9
11 liver/biliary system MP:0005370 10.08 WT1 BMP5 BMP4 CTNNB1 FURIN FGFR2
12 hearing/vestibular/ear MP:0005377 10.07 WNT7A BMP5 BMP4 CTNNB1 FGFR2 SOX9
13 no phenotypic analysis MP:0003012 10.02 WT1 AMH AMHR2 BMP4 CTNNB1 FGFR2
14 normal MP:0002873 10.02 WNT7A WT1 BMP4 CTNNB1 FURIN FGFR2
15 reproductive system MP:0005389 10 WT1 WNT7A AMHR2 BMP5 BMP15 BMP4
16 muscle MP:0005369 9.98 WT1 BMP4 FGFR2 CTNNB1 KIT SOX9
17 neoplasm MP:0002006 9.95 WT1 AMH AMHR2 CTNNB1 FGFR2 KIT
18 renal/urinary system MP:0005367 9.91 WT1 AMHR2 BMP5 BMP4 FGFR2 KIT
19 respiratory system MP:0005388 9.61 WT1 AMHR2 BMP5 BMP4 CTNNB1 FGFR2
20 skeleton MP:0005390 9.28 WNT7A BMP4 BMP5 CTNNB1 INSL3 FGFR2

Drugs & Therapeutics for Persistent Mullerian Duct Syndrome

Search Clinical Trials , NIH Clinical Center for Persistent Mullerian Duct Syndrome

Cochrane evidence based reviews: persistent mullerian duct syndrome

Genetic Tests for Persistent Mullerian Duct Syndrome

Genetic tests related to Persistent Mullerian Duct Syndrome:

# Genetic test Affiliating Genes
1 Persistent Mullerian Duct Syndrome 29 AMH AMHR2

Anatomical Context for Persistent Mullerian Duct Syndrome

MalaCards organs/tissues related to Persistent Mullerian Duct Syndrome:

41
Uterus, Testes, Cervix, Testis, Kidney

Publications for Persistent Mullerian Duct Syndrome

Articles related to Persistent Mullerian Duct Syndrome:

(show top 50) (show all 69)
# Title Authors Year
1
Transverse testicular ectopia with persistent mullerian duct syndrome. ( 29669771 )
2018
2
REPLY BY THE AUTHORS: Re: Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management. ( 28792190 )
2017
3
Re: Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management. ( 28792189 )
2017
4
Persistent Mullerian Duct Syndrome Presenting in an Incarcerated Recurrent Inguinal Hernia with Hydrocele. ( 28331809 )
2017
5
MRI findings of Persistent Mullerian Duct Syndrome: A Rare Case Report. ( 28764266 )
2017
6
A rare case of male pseudohermaphroditism-persistent mullerian duct syndrome with transverse testicular ectopia - Case report and review of literature. ( 28645010 )
2017
7
Persistent Mullerian Duct Syndrome with Embryonal Cell Carcinoma along with Ectopic Cross Fused Kidney. ( 26894123 )
2016
8
Persistent mullerian duct syndrome presenting as retractile testis with hypospadias: A rare entity. ( 27326401 )
2016
9
Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management. ( 27532119 )
2016
10
Persistent mullerian duct syndrome: A 24-year experience. ( 27329391 )
2016
11
Persistent Mullerian Duct Syndrome with Ovarian Endometriosis-A Rare Case Report. ( 27042476 )
2016
12
A case of testicular seminoma in persistent Mullerian duct syndrome with transverse testicular ectopia. ( 25504517 )
2015
13
A novel mutation of AMH in three siblings with persistent Mullerian duct syndrome. ( 26181047 )
2015
14
Female form of persistent mullerian duct syndrome: Rare entity. ( 25657558 )
2015
15
Acute urinary retention caused by seminoma in a case of persistent Mullerian duct syndrome. ( 25673601 )
2015
16
Laparoscopic management of transverse testicular ectopia with persistent mullerian duct syndrome. ( 26195884 )
2015
17
Laparoscopic hysterectomy with bilateral orchidectomy for Persistent Mullerian duct syndrome with seminoma testes: Case report. ( 26622120 )
2015
18
Persistent Mullerian Duct Syndrome with Transverse Testicular Ectopia. ( 27512542 )
2015
19
Persistent mullerian duct syndrome: A case report and review of the literature. ( 25143891 )
2014
20
Persistent mullerian duct syndrome with transverse testicular ectopia: rare entity. ( 24783120 )
2014
21
Persistent Mullerian duct syndrome with transverse testicular ectopia and seminoma. ( 24554220 )
2014
22
Excision of Mullerian duct remnant for persistent Mullerian duct syndrome provides favorable short- and mid-term outcomes. ( 24594348 )
2014
23
Indirect inguinal hernia with uterine tissue in a male: A case of persistent Mullerian duct syndrome and literature review. ( 23671501 )
2013
24
Persistent Mullerian Duct Syndrome: an interesting case report. ( 24045516 )
2013
25
Robot-assisted Laparoscopic Hysterectomy, Gonadal Biopsy, and Orchiopexies in an Infant With Persistent Mullerian Duct Syndrome. ( 24246315 )
2013
26
Persistent Mullerian duct syndrome with transverse testicular ectopia: rare presentation of inguinal hernia. ( 23801478 )
2013
27
A novel mutation of anti-Mullerian hormone gene in Persistent Mullerian Duct Syndrome presented with bilateral cryptorchidism: a case report. ( 23611722 )
2013
28
Persistent Mullerian duct syndrome: a rare cause of unilateral cryptorchidism. ( 22977013 )
2012
29
Persistent mullerian duct syndrome in a patient with bilateral cryptorchid testes with seminoma. ( 23162363 )
2012
30
Male form of persistent Mullerian duct syndrome type I (hernia uteri inguinalis) presenting as an obstructed inguinal hernia: a case report. ( 22185203 )
2011
31
Persistent Mullerian duct syndrome with testicular seminoma: A report of two cases. ( 22022070 )
2011
32
Persistent mullerian duct syndrome in adult men diagnosed using laparoscopy. ( 21256537 )
2011
33
Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour. ( 18954385 )
2010
34
Testicular fusion in a patient with transverse testicular ectopia and persistent mullerian duct syndrome. ( 20092878 )
2010
35
Persistent mullerian duct syndrome. ( 20352001 )
2010
36
Persistent Mullerian duct syndrome: a case-based algorithm. ( 20509098 )
2010
37
Transverse testicular ectopia and persistent Mullerian duct syndrome: video-assisted treatment. ( 19360556 )
2010
38
Persistent Mullerian duct syndrome: a case report and review of the literature. ( 20859029 )
2010
39
Persistent mullerian duct syndrome with an irreducible inguinal hernia. ( 20027561 )
2009
40
Laparoscopic management of persistent mullerian duct syndrome. ( 19735801 )
2009
41
Natural mutations of the anti-Mullerian hormone type II receptor found in persistent Mullerian duct syndrome affect ligand binding, signal transduction and cellular transport. ( 19457927 )
2009
42
Combined persistent Mullerian Duct Syndrome, Transverse Testicular Ectopia and Mosaic Klinefelter's Syndrome. ( 18760051 )
2008
43
Tuberculosis of transverse testicular ectopic testis associated with persistent mullerian duct syndrome. ( 18474165 )
2008
44
Three novel AMH gene mutations in a patient with persistent mullerian duct syndrome and normal AMH serum dosage. ( 18547961 )
2008
45
Transverse testicular ectopia associated with persistent Mullerian duct syndrome - the role of imaging. ( 18559894 )
2008
46
Persistent Mullerian duct syndrome with transverse testicular ectopia presenting in an irreducible recurrent inguinal hernia. ( 17902529 )
2007
47
Persistent mullerian duct syndrome and transverse testicular ectopia: embryology, presentation, and management. ( 18082721 )
2007
48
Persistent mullerian duct syndrome with transverse testicular ectopia. ( 17333518 )
2007
49
Persistent mullerian duct syndrome with transverse testicular ectopia. ( 15730845 )
2005
50
Persistent Mullerian duct syndrome with bilateral abdominal testis: surgical approach and review of the literature. ( 18947583 )
2005

Variations for Persistent Mullerian Duct Syndrome

ClinVar genetic disease variations for Persistent Mullerian Duct Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 AMH NM_000479.4(AMH): c.146G> T (p.Ser49Ile) single nucleotide variant Benign rs10407022 GRCh37 Chromosome 19, 2249477: 2249477
2 AMH NM_000479.4(AMH): c.146G> T (p.Ser49Ile) single nucleotide variant Benign rs10407022 GRCh38 Chromosome 19, 2249478: 2249478
3 AMH NM_000479.4(AMH): c.1239T> A (p.Gly413=) single nucleotide variant Benign rs7252789 GRCh38 Chromosome 19, 2251513: 2251513
4 AMH NM_000479.4(AMH): c.1239T> A (p.Gly413=) single nucleotide variant Benign rs7252789 GRCh37 Chromosome 19, 2251512: 2251512
5 AMHR2 NM_020547.3(AMHR2): c.622-6C> T single nucleotide variant Benign rs2071558 GRCh37 Chromosome 12, 53819467: 53819467
6 AMHR2 NM_020547.3(AMHR2): c.622-6C> T single nucleotide variant Benign rs2071558 GRCh38 Chromosome 12, 53425683: 53425683

Expression for Persistent Mullerian Duct Syndrome

Search GEO for disease gene expression data for Persistent Mullerian Duct Syndrome.

Pathways for Persistent Mullerian Duct Syndrome

GO Terms for Persistent Mullerian Duct Syndrome

Cellular components related to Persistent Mullerian Duct Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell surface GO:0009986 9.55 FGFR2 FURIN KIT NOTCH2 WNT7A
2 extracellular region GO:0005576 9.28 AMH BMP15 BMP4 BMP5 FGFR2 FURIN
3 nuclear transcription factor complex GO:0044798 8.96 CTNNB1 SOX9

Biological processes related to Persistent Mullerian Duct Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 92)
# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.98 BMP4 BMP5 CTNNB1 SOX9
2 positive regulation of gene expression GO:0010628 9.95 AMH BMP4 CTNNB1 KIT NR5A1 SOX9
3 kidney development GO:0001822 9.94 BMP4 CTNNB1 WT1
4 lung development GO:0030324 9.94 BMP4 CTNNB1 FGFR2
5 ossification GO:0001503 9.94 BMP4 BMP5 SOX9
6 positive regulation of transcription, DNA-templated GO:0045893 9.92 BMP15 BMP4 CTNNB1 NR5A1 SOX9 SRY
7 hemopoiesis GO:0030097 9.91 CTNNB1 KIT NOTCH2
8 somatic stem cell population maintenance GO:0035019 9.91 KIT SOX9 WNT7A
9 negative regulation of epithelial cell proliferation GO:0050680 9.9 BMP4 FGFR2 SOX9
10 SMAD protein signal transduction GO:0060395 9.89 BMP15 BMP4 BMP5
11 embryonic digit morphogenesis GO:0042733 9.89 BMP4 CTNNB1 WNT7A
12 cell development GO:0048468 9.89 BMP15 BMP4 BMP5
13 cellular response to transforming growth factor beta stimulus GO:0071560 9.89 FGFR2 SOX9 WNT7A
14 regulation of MAPK cascade GO:0043408 9.89 BMP15 BMP4 BMP5
15 stem cell population maintenance GO:0019827 9.88 CTNNB1 KIT NOTCH2
16 cartilage development GO:0051216 9.87 BMP4 BMP5 SOX9 WNT7A
17 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.86 BMP15 BMP4 BMP5
18 regulation of cell differentiation GO:0045595 9.86 BMP4 CTNNB1 SOX9
19 ureteric bud development GO:0001657 9.86 BMP4 FGFR2 WT1
20 cell fate commitment GO:0045165 9.85 BMP4 FGFR2 SOX9 WNT7A
21 positive regulation of epithelial cell proliferation GO:0050679 9.84 BMP4 BMP5 FGFR2 SOX9
22 chondrocyte differentiation GO:0002062 9.83 BMP4 SOX9 WNT7A
23 male gonad development GO:0008584 9.83 AMHR2 KIT NR5A1 SOX9 WT1
24 epithelial to mesenchymal transition GO:0001837 9.82 CTNNB1 FGFR2 SOX9
25 embryonic hindlimb morphogenesis GO:0035116 9.8 BMP4 CTNNB1 WNT7A
26 branching involved in ureteric bud morphogenesis GO:0001658 9.8 BMP4 CTNNB1 SOX9 WT1
27 tissue development GO:0009888 9.79 BMP4 NR5A1 WT1
28 positive regulation of mesenchymal cell proliferation GO:0002053 9.79 CTNNB1 FGFR2 SOX9
29 adrenal gland development GO:0030325 9.77 NR5A1 WT1
30 cell fate determination GO:0001709 9.77 CTNNB1 NOTCH2
31 anterior/posterior axis specification GO:0009948 9.77 BMP4 CTNNB1
32 positive regulation of endothelial cell differentiation GO:0045603 9.77 BMP4 CTNNB1
33 BMP signaling pathway GO:0030509 9.77 AMH AMHR2 BMP15 BMP4 BMP5
34 positive regulation of cartilage development GO:0061036 9.76 BMP4 SOX9
35 smooth muscle cell differentiation GO:0051145 9.76 BMP4 CTNNB1
36 regulation of osteoblast differentiation GO:0045667 9.76 CTNNB1 FGFR2
37 mesodermal cell differentiation GO:0048333 9.76 BMP4 FGFR2
38 gonad development GO:0008406 9.76 AMH WT1
39 negative regulation of pri-miRNA transcription by RNA polymerase II GO:1902894 9.76 BMP4 SOX9
40 male genitalia development GO:0030539 9.76 BMP5 CTNNB1 WT1
41 male sex determination GO:0030238 9.75 SOX9 SRY
42 type B pancreatic cell development GO:0003323 9.75 BMP4 BMP5
43 morphogenesis of embryonic epithelium GO:0016331 9.75 CTNNB1 FGFR2
44 limb bud formation GO:0060174 9.75 FGFR2 SOX9
45 negative regulation of chondrocyte differentiation GO:0032331 9.75 BMP4 CTNNB1 SOX9
46 somatic stem cell division GO:0048103 9.74 KIT WNT7A
47 regulation of smooth muscle cell proliferation GO:0048660 9.74 BMP4 CTNNB1
48 pulmonary valve morphogenesis GO:0003184 9.74 BMP4 NOTCH2
49 membranous septum morphogenesis GO:0003149 9.74 BMP4 FGFR2
50 lung-associated mesenchyme development GO:0060484 9.73 CTNNB1 FGFR2

Molecular functions related to Persistent Mullerian Duct Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protease binding GO:0002020 9.54 FURIN INSL3 KIT
2 cytokine activity GO:0005125 9.46 BMP15 BMP4 BMP5 WNT7A
3 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding GO:0003705 9.43 NR5A1 SOX9 SRY
4 BMP receptor binding GO:0070700 9.32 BMP4 BMP5
5 growth factor activity GO:0008083 9.26 AMH BMP15 BMP4 BMP5
6 transforming growth factor beta receptor binding GO:0005160 8.92 AMH BMP15 BMP4 BMP5

Sources for Persistent Mullerian Duct Syndrome

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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44 MeSH
45 MESH via Orphanet
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49 NCI
50 NCIt
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
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74 UMLS via Orphanet
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