PHA
MCID: PLG001
MIFTS: 51

Pelger-Huet Anomaly (PHA)

Categories: Blood diseases, Bone diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Pelger-Huet Anomaly

MalaCards integrated aliases for Pelger-Huet Anomaly:

Name: Pelger-Huet Anomaly 56 12 52 73 36 13 54 43 15 39 17 71
Pha 56 52 73
Pelger-Huët Anomaly 29 6
Ovoid Neutrophil Nuclei, Developmental Delay, Epilepsy and Skeletal Abnormalities 52
Pelger-Huet Nuclear Anomaly 52
Pelger Huet Anomaly 52

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
allelic to hydropic and prenatally lethal chondrodystrophy
increased frequency in vastebotten county in northern sweden and gelenau in southeastern germany


HPO:

31
pelger-huet anomaly:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Pelger-Huet Anomaly

NIH Rare Diseases : 52 Pelger-Huet anomaly (PHA) is an inherited blood condition in which the nuclei of several types of white blood cells (neutrophils and eosinophils ) have unusual shape (bilobed, peanut or dumbbell-shaped instead of the normal trilobed shape) and unusual structure (coarse and lumpy). Click here to view a picture of these cells seen under the microscope. PHA is considered to be a benign disorder in most instances, as individuals with PHA are typically healthy. PHA is caused by mutations in the LBR gene . It is suspected that mutations within the LBR gene are responsible for a spectrum of disorders including isolated PHA; PHA with mild skeletal symptoms; and Hydrops, Ectopic calcification, Moth-eaten skeletal dysplasia (HEM) . PHA was previously thought to be inherited in an autosomal dominant manner; however, co-dominant inheritance has been suggested as well. It is important to distinguish PHA from acquired or pseudo-Pelger-Huet anomaly, which may be found in individuals with certain types of leukemia or myelodysplastic syndromes . Diagnosis is made based on characteristic appearance of white blood cell nuclei identified by a blood smear . Most individuals with PHA do not require treatment as they do not have symptoms.

MalaCards based summary : Pelger-Huet Anomaly, also known as pha, is related to laminopathy and muscular dystrophy. An important gene associated with Pelger-Huet Anomaly is LBR (Lamin B Receptor), and among its related pathways/superpathways are Cell Cycle, Mitotic and Transport of the SLBP independent Mature mRNA. Affiliated tissues include neutrophil, myeloid and bone, and related phenotypes are abnormality of chromosome segregation and intellectual disability

Disease Ontology : 12 A hematopoietic system disease characterized by white blood cells with unusually shaped nuclei that has material basis in heterozygous mutation in LBR on chromosome 1q42.12.

KEGG : 36 Pelger-Huet anomaly is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes with skeletal abnormalities.

UniProtKB/Swiss-Prot : 73 Pelger-Huet anomaly: An autosomal dominant inherited abnormality of granulocytes, characterized by abnormal ovoid shape, reduced nuclear segmentation and an apparently looser chromatin structure.

Wikipedia : 74 Pelger-Huët anomaly is a blood laminopathy associated with the lamin B receptor, wherein several types... more...

More information from OMIM: 169400

Related Diseases for Pelger-Huet Anomaly

Diseases in the Pelger-Huet Anomaly family:

Pseudo Pelger-Huet Anomaly

Diseases related to Pelger-Huet Anomaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 308)
# Related Disease Score Top Affiliating Genes
1 laminopathy 30.6 SUN1 LMNA EMD
2 muscular dystrophy 29.2 SYNE1 SUN1 LMNB2 LMNB1 LMNA LBR
3 short stature, optic nerve atrophy, and pelger-huet anomaly 13.1
4 pelger-huet anomaly with mild skeletal anomalies 13.1
5 pseudo pelger-huet anomaly 12.8
6 short stature with optic atrophy and pelger-huët anomaly syndrome 12.8
7 hemifacial atrophy, progressive 12.0
8 pseudohypoaldosteronism, type i, autosomal dominant 12.0
9 pseudohypoaldosteronism, type i, autosomal recessive 11.5
10 pseudohypoaldosteronism 11.5
11 immunodeficiency-centromeric instability-facial anomalies syndrome 1 11.2
12 t-cell immunodeficiency, congenital alopecia, and nail dystrophy 11.2
13 myelodysplastic syndrome 10.7
14 myelofibrosis 10.5
15 leukemia, acute myeloid 10.5
16 polydactyly 10.5
17 acute leukemia 10.5
18 myeloid leukemia 10.5
19 chromosomal triplication 10.5
20 familial mediterranean fever 10.5
21 3-methylglutaconic aciduria, type iii 10.5
22 autoimmune disease 3 10.5
23 erythroleukemia, familial 10.4
24 leukemia, chronic lymphocytic 10.4
25 neutrophil migration 10.4
26 chromosome 2q35 duplication syndrome 10.4
27 myeloma, multiple 10.4
28 polycythemia vera 10.4
29 muscular dystrophy, limb-girdle, autosomal dominant 1 10.4
30 leukemia, chronic myeloid 10.4
31 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.4
32 hemopericardium 10.4
33 patau syndrome 10.4
34 pericardial effusion 10.4
35 leukemia 10.4
36 pancytopenia 10.4
37 mycoplasma pneumoniae pneumonia 10.4
38 colon adenocarcinoma 10.4
39 epidermolysis bullosa 10.4
40 adenocarcinoma 10.4
41 epidermolysis bullosa dystrophica 10.4
42 pneumonia 10.4
43 polycythemia 10.4
44 albinism 10.4
45 familial acute myeloid leukemia with mutated cebpa 10.4
46 refractory anemia 10.4
47 red cell aplasia 10.4
48 cleft palate, isolated 10.3
49 light fixation seizure syndrome 10.3
50 mycobacterium tuberculosis 1 10.3

Symptoms & Phenotypes for Pelger-Huet Anomaly

Human phenotypes related to Pelger-Huet Anomaly:

31 (show all 33)
# Description HPO Frequency HPO Source Accession
1 abnormality of chromosome segregation 31 hallmark (90%) HP:0002916
2 intellectual disability 31 very rare (1%) HP:0001249
3 depressed nasal bridge 31 very rare (1%) HP:0005280
4 gingival overgrowth 31 very rare (1%) HP:0000212
5 hypertelorism 31 very rare (1%) HP:0000316
6 kyphosis 31 very rare (1%) HP:0002808
7 macrocephaly 31 very rare (1%) HP:0000256
8 abnormality of the dentition 31 very rare (1%) HP:0000164
9 umbilical hernia 31 very rare (1%) HP:0001537
10 failure to thrive 31 very rare (1%) HP:0001508
11 frontal bossing 31 very rare (1%) HP:0002007
12 strabismus 31 very rare (1%) HP:0000486
13 recurrent otitis media 31 very rare (1%) HP:0000403
14 short 4th metacarpal 31 very rare (1%) HP:0010044
15 short 5th metacarpal 31 very rare (1%) HP:0010047
16 thrombocytopenia 31 very rare (1%) HP:0001873
17 ventricular septal defect 31 very rare (1%) HP:0001629
18 pes cavus 31 very rare (1%) HP:0001761
19 neutropenia 31 very rare (1%) HP:0001875
20 eczema 31 very rare (1%) HP:0000964
21 mild short stature 31 very rare (1%) HP:0003502
22 median cleft palate 31 very rare (1%) HP:0009099
23 foot dorsiflexor weakness 31 very rare (1%) HP:0009027
24 upper limb undergrowth 31 very rare (1%) HP:0009824
25 lower limb hyperreflexia 31 very rare (1%) HP:0002395
26 giant platelets 31 very rare (1%) HP:0001902
27 short 3rd metacarpal 31 very rare (1%) HP:0010041
28 lower limb hypertonia 31 very rare (1%) HP:0006895
29 bilateral tonic-clonic seizure 31 very rare (1%) HP:0002069
30 global developmental delay 31 HP:0001263
31 prominent forehead 31 HP:0011220
32 polydactyly 31 HP:0010442
33 hyposegmentation of neutrophil nuclei 31 HP:0011447

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly (homozygote)

Cardiovascular Heart:
ventricular septal defect (homozygote)

Neurologic Central Nervous System:
developmental delay (homozygote)
seizure disorder (homozygote)

Head And Neck Face:
prominent forehead (homozygote)

Skeletal Hands:
polydactyly (homozygote)
short metacarpals (homozygote)

Hematology:
hypolobulated (bilobed or rod-like) granulocyte nuclei (heterozygote)
ovoid granulocyte nuclei (homozygote)
coarse granulocyte chromatin

Clinical features from OMIM:

169400

GenomeRNAi Phenotypes related to Pelger-Huet Anomaly according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00106-A-0 9.62 AKAP8L U2AF1
2 Decreased viability GR00221-A-1 9.62 AKAP8L
3 Decreased viability GR00221-A-2 9.62 AKAP8L
4 Decreased viability GR00221-A-3 9.62 AKAP8L
5 Decreased viability GR00240-S-1 9.62 LEXM LMNA
6 Decreased viability GR00249-S 9.62 DISP1 LBR LMNA
7 Decreased viability GR00381-A-1 9.62 DISP1
8 Decreased viability GR00386-A-1 9.62 LMNA LUC7L2 SUN1 TM7SF2
9 Decreased viability GR00402-S-2 9.62 LBR LMNB1 NUP133 STX18 U2AF1

MGI Mouse Phenotypes related to Pelger-Huet Anomaly:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.11 DISP1 EMD LBR LEMD2 LEMD3 LEXM
2 cardiovascular system MP:0005385 10.06 DISP1 EMD LEMD2 LEMD3 LMNA NBAS
3 growth/size/body region MP:0005378 10.06 DISP1 LBR LEMD2 LMNA LMNB1 LMNB2
4 homeostasis/metabolism MP:0005376 10.03 DISP1 EMD LBR LMNA LMNB1 LMNB2
5 mortality/aging MP:0010768 10 DISP1 LBR LEMD2 LEMD3 LEXM LMNA
6 muscle MP:0005369 9.56 DISP1 EMD LEMD2 LMNA LMNB1 LMNB2
7 nervous system MP:0003631 9.36 DISP1 LBR LEMD2 LMNA LMNB1 LMNB2

Drugs & Therapeutics for Pelger-Huet Anomaly

Search Clinical Trials , NIH Clinical Center for Pelger-Huet Anomaly

Cochrane evidence based reviews: pelger-huet anomaly

Genetic Tests for Pelger-Huet Anomaly

Genetic tests related to Pelger-Huet Anomaly:

# Genetic test Affiliating Genes
1 Pelger-Huët Anomaly 29 LBR

Anatomical Context for Pelger-Huet Anomaly

MalaCards organs/tissues related to Pelger-Huet Anomaly:

40
Neutrophil, Myeloid, Bone, Liver, Bone Marrow, Retina, Small Intestine

Publications for Pelger-Huet Anomaly

Articles related to Pelger-Huet Anomaly:

(show top 50) (show all 236)
# Title Authors PMID Year
1
Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly). 61 6 56
12118250 2002
2
Lamin B-receptor mutations in Pelger-Huët anomaly. 61 54 6
14617022 2003
3
Autosomal recessive HEM/Greenberg skeletal dysplasia is caused by 3 beta-hydroxysterol delta 14-reductase deficiency due to mutations in the lamin B receptor gene. 54 6 61
12618959 2003
4
Mutations at the mouse ichthyosis locus are within the lamin B receptor gene: a single gene model for human Pelger-Huët anomaly. 61 56
12490533 2003
5
Association of acquired Pelger-Huet anomaly with taxoid therapy. 61 56
8611447 1996
6
Congenital Pelger-Huet anomaly in triplets. 61 56
3348208 1988
7
Acute lymphoblastic leukaemia in a child with familial Pelger-Huet anomaly. 56 61
3475111 1987
8
Pelger-Huët anomaly in cats. 56 61
4035941 1985
9
The Pelger-Huët anomaly of leukocytes: description of a Quebec kindred. 56 61
5686316 1968
10
Pelger-Huet anomaly of leukocytes. Report of a case and survey of incidence. 56 61
14467172 1962
11
The Pelger-Huët anomaly in three families and its use in determining the disappearance of transfused neutrophils from the peripheral blood. 61 56
13618374 1959
12
Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein. 6
21327084 2010
13
Congenital abnormalities reported in Pelger-Huët homozygosity as compared to Greenberg/HEM dysplasia: highly variable expression of allelic phenotypes. 56
14684694 2003
14
A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. 56
10942370 2000
15
Acquired Pelger-Huët nuclear anomaly with tuberculosis. 56
7053717 1982
16
Studies on the Pelger anomaly in Iceland. 56
848354 1977
17
Abnormal nuclear morphology of leukocytes in the mouse mutant ichthyosis. 56
1101484 1975
18
The Pelger anomaly of leukocytes: forty-one cases in seven families. 56
13913617 1962
19
The Pelger-anomaly in man and rabbit; a mendelian character of the nuclei of the leucocytes. 56
15436969 1950
20
[Nuclear abnormalities in Pelger-Huet anomaly; progress in blood cell morphology]. 54 61
15724491 2005
21
Role of nuclear lamins in nuclear segmentation of human neutrophils. 54 61
10816760 1999
22
A new case of Greenberg dysplasia and literature review suggest that Greenberg dysplasia, dappled diaphyseal dysplasia, and Astley-Kendall dysplasia are allelic disorders. 61
32304187 2020
23
Defining clinical subgroups and genotype-phenotype correlations in NBAS-associated disease across 110 patients. 61
31761904 2020
24
Acquired Pelger-Huët anomaly in a patient treated with valganciclovir. 61
31611226 2019
25
Familial case of hereditary Pelger-Huët anomaly. 61
31154564 2019
26
The Pseudo-Pelger huët Cell as a Retrospective Dosimeter: Analysis of a Radium Dial Painter Cohort. 61
29595755 2019
27
SOPH syndrome in three affected individuals showing similarities with progeroid cutis laxa conditions in early infancy. 61
31015584 2019
28
A family with congenital Pelger-Huët anomaly. 61
31041635 2019
29
Necrobiotic xanthogranuloma (without paraproteinemia) in a patient with Pelger-Huët anomaly. 61
30588610 2019
30
Lamin B receptor-related disorder is associated with a spectrum of skeletal dysplasia phenotypes. 61
30448303 2019
31
A novel case of Greenberg dysplasia and genotype-phenotype correlation analysis for LBR pathogenic variants: An instructive example of one gene-multiple phenotypes. 61
30561119 2019
32
Novel neuroblastoma amplified sequence (NBAS) mutations in a Japanese boy with fever-triggered recurrent acute liver failure. 61
30622725 2019
33
SOPH Syndrome with Growth Hormone Deficiency, Normal Bone Age, and Novel Compound Heterozygous Mutations in NBAS. 61
30592236 2018
34
Stodtmeister Cells (Polymorphs with Pelger-Huët Anomaly) Showing "Faggots" in Mixed Phenotypic Acute Leukemia (T/Myeloid). 61
29398816 2018
35
[Short stature, optic nerve atrophy and Pelger-Huët anomaly syndrome with antibody immunodeficiency and aplastic anemia: a case report and literature review]. 61
29262476 2017
36
High diagnostic yield of clinically unidentifiable syndromic growth disorders by targeted exome sequencing. 61
28425089 2017
37
Image analysis of neutrophil nuclear morphology: Learning about phenotypic range and its reliable analysis from patients with pelger-Huët-anomaly and treated with colchicine. 61
27684937 2017
38
Lamin B Receptor: Interplay between Structure, Function and Localization. 61
28858257 2017
39
The Pseudo-Pelger HuËt Cell-A New Permanent Radiation Biomarker. 61
28121725 2017
40
Acute Liver Failure Meets SOPH Syndrome: A Case Report on an Intermediate Phenotype. 61
28031453 2017
41
Hyposplenic changes and pseudo-Pelger-Huët anomaly following allogeneic stem cell transplantation. 61
27723081 2017
42
Foveal hypoplasia in short stature with optic atrophy and Pelger-Huët anomaly syndrome with neuroblastoma-amplified sequence (NBAS) gene mutation. 61
28115293 2017
43
Compound heterozygous variants in NBAS as a cause of atypical osteogenesis imperfecta. 61
27789416 2017
44
[Population frequency and age of mutation G5741→A in gene NBAS which is a cause of SOPH syndrome in Sakha (Yakutia) Republic]. 61
29369590 2016
45
Alterations in nuclear structure promote lupus autoimmunity in a mouse model. 61
27483354 2016
46
Familial Pelger-Huet Anomaly. 61
27408433 2016
47
Transient Deformation of Neutrophils in Kawasaki Disease. 61
27039225 2016
48
The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations. 61
27336722 2016
49
[Acquired Pelger-Huët anomaly/abnormal chromatin clumping of granulocytes after allogeneic hematopoietic stem cell transplantation for acute myeloid leukaemia: medication or relapse? ]. 61
26878615 2016
50
Pelger-Huët anomaly and Greenberg skeletal dysplasia: LBR-associated diseases of cholesterol metabolism. 61
27830109 2016

Variations for Pelger-Huet Anomaly

ClinVar genetic disease variations for Pelger-Huet Anomaly:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 LBR NM_002296.4(LBR):c.1565-10_1565-5delshort repeat Pathogenic 9527 rs886037616 1:225592233-225592238 1:225404531-225404536
2 LBR NM_002296.4(LBR):c.166-2A>GSNV Pathogenic 9528 1:225609981-225609981 1:225422279-225422279
3 LBR NM_002296.4(LBR):c.1599_1605delinsCTAGAAG (p.Leu534_Leu535delinsTer)indel Pathogenic 9529 rs387906416 1:225592188-225592194 1:225404486-225404492
4 LBR NM_002296.4(LBR):c.356C>T (p.Pro119Leu)SNV Pathogenic 9530 1:225609789-225609789 1:225422087-225422087
5 LBR NM_002296.4(LBR):c.1484-9A>GSNV Pathogenic 9531 1:225592417-225592417 1:225404715-225404715
6 LBR NM_002296.4(LBR):c.1706C>G (p.Pro569Arg)SNV Pathogenic 9532 1:225591147-225591147 1:225403445-225403445
7 LBR NM_002296.4(LBR):c.32_35del (p.Val11fs)deletion Pathogenic 100902 rs863223326 1:225611743-225611746 1:225424041-225424044
8 LBR NM_002296.4(LBR):c.1747C>T (p.Arg583Ter)SNV Conflicting interpretations of pathogenicity 369680 rs1057516045 1:225591106-225591106 1:225403404-225403404
9 LBR NM_002296.4(LBR):c.1366C>G (p.Leu456Val)SNV Uncertain significance 426800 rs377110126 1:225594483-225594483 1:225406781-225406781

UniProtKB/Swiss-Prot genetic disease variations for Pelger-Huet Anomaly:

73
# Symbol AA change Variation ID SNP ID
1 LBR p.Pro119Leu VAR_017841 rs137852605
2 LBR p.Pro569Arg VAR_017842 rs137852606

Expression for Pelger-Huet Anomaly

Search GEO for disease gene expression data for Pelger-Huet Anomaly.

Pathways for Pelger-Huet Anomaly

Pathways related to Pelger-Huet Anomaly according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.02 SYNE1 SUN1 NUP133 LMNB1 LMNA LEMD3
2
Show member pathways
12.93 NUP133 LMNB1 LMNA LEMD3 LEMD2 EMD
3
Show member pathways
12.35 NUP133 LMNB1 LMNA LEMD3 LEMD2 EMD
4 12.19 LMNB2 LMNB1 LMNA EMD
5
Show member pathways
12.13 SYNE1 SUN1 LMNB1 LMNA
6
Show member pathways
12.06 NUP133 LMNB1 LMNA LEMD3 LEMD2 EMD
7
Show member pathways
11.89 LMNB2 LMNB1 LMNA
8
Show member pathways
11.22 LMNB2 LMNB1 LMNA
9
Show member pathways
10.54 LMNB1 LMNA LEMD3 LEMD2 EMD

GO Terms for Pelger-Huet Anomaly

Cellular components related to Pelger-Huet Anomaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 10.22 U2AF1 SYNE1 SUN1 NUP133 LUC7L2 LMNB2
2 nuclear envelope GO:0005635 9.81 SYNE1 SUN1 NUP133 LMNB2 LMNB1 LMNA
3 nuclear speck GO:0016607 9.73 U2AF1 LUC7L2 LMNA AKAP8L
4 nuclear membrane GO:0031965 9.65 SYNE1 SUN1 NUP133 LMNB2 LMNB1 LMNA
5 integral component of nuclear inner membrane GO:0005639 9.56 SUN1 LEMD3 LEMD2 LBR
6 lamin filament GO:0005638 9.5 LMNB2 LMNB1 LMNA
7 nuclear outer membrane GO:0005640 9.46 SYNE1 EMD
8 meiotic nuclear membrane microtubule tethering complex GO:0034993 9.37 SYNE1 SUN1
9 nuclear inner membrane GO:0005637 9.23 TM7SF2 SUN1 LMNB2 LMNB1 LEMD3 LEMD2

Biological processes related to Pelger-Huet Anomaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear-transcribed mRNA catabolic process GO:0000956 9.43 NBAS DHX34
2 mitotic nuclear envelope reassembly GO:0007084 9.4 LMNA EMD
3 regulation of intracellular signal transduction GO:1902531 9.37 LEMD3 LEMD2
4 cytoskeletal anchoring at nuclear membrane GO:0090286 9.32 SYNE1 SUN1
5 negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:2000623 9.26 NBAS DHX34
6 nuclear matrix anchoring at nuclear membrane GO:0090292 9.16 SYNE1 SUN1
7 nucleus organization GO:0006997 9.13 SYNE1 LMNA LEMD3
8 nuclear envelope organization GO:0006998 8.92 SUN1 LMNA LEMD3 LEMD2

Molecular functions related to Pelger-Huet Anomaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.26 TM7SF2 LBR
2 oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor GO:0016628 9.16 TM7SF2 LBR
3 delta14-sterol reductase activity GO:0050613 8.96 TM7SF2 LBR
4 lamin binding GO:0005521 8.92 SYNE1 SUN1 LBR AKAP8L

Sources for Pelger-Huet Anomaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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30 HMDB
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32 ICD10
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34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
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44 MESH via Orphanet
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50 NDF-RT
53 NINDS
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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