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MCID: LPR012
MIFTS: 33

Leopard Syndrome 1

Categories: Genetic diseases, Cardiovascular diseases, Rare diseases, Reproductive diseases, Ear diseases
Genes Variations Tissues Related diseases Publications Symptoms & Phenotypes
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Aliases & Classifications for Leopard Syndrome 1

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MalaCards integrated aliases for Leopard Syndrome 1:

Name: Leopard Syndrome 1 57 75 29 13 6
Multiple Lentigines 29 73
Lprd1 57 75
Lentiginosis, Cardiomyopathic 57
Multiple Lentigines Syndrome 57
Leopard Syndrome, Type 1 40
Leopard Syndrome 73

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
leopard is an acronym: lentigines, ekg abnormalities, ocular hypertelorism, obstructive cardiomyopathy, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness
allelic to noonan syndrome


HPO:

32
leopard syndrome 1:
Inheritance autosomal dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Cardiovascular diseases Reproductive diseases Ear diseases
See all MalaCards categories (disease lists)


Sources

Summaries for Leopard Syndrome 1

About this section
OMIM : 57 LEOPARD is an acronym for the manifestations of this syndrome as listed by Gorlin et al. (1969): multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness. (151100)

MalaCards based summary : Leopard Syndrome 1, also known as multiple lentigines, is related to leopard syndrome and noonan syndrome with multiple lentigines, and has symptoms including hyposmia An important gene associated with Leopard Syndrome 1 is PTPN11 (Protein Tyrosine Phosphatase, Non-Receptor Type 11). Affiliated tissues include ovary and heart, and related phenotypes are hypertelorism and low-set ears

UniProtKB/Swiss-Prot : 75 LEOPARD syndrome 1: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.

Sources

Related Diseases for Leopard Syndrome 1

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Diseases in the Leopard Syndrome family:

Leopard Syndrome 1 Leopard Syndrome 2
Leopard Syndrome 3

Diseases related to Leopard Syndrome 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 leopard syndrome 11.5
2 noonan syndrome with multiple lentigines 11.2

Sources

Symptoms & Phenotypes for Leopard Syndrome 1

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Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
ptosis
strabismus
epicanthal folds

Head And Neck Neck:
short neck
pterygium colli

Growth Weight:
short stature

Head And Neck Mouth:
cleft palate

Cardiovascular Heart:
bundle branch block
subaortic stenosis
pulmonic stenosis (40%)
superior ekg axis (-60 degrees to -120 degrees)
hypertrophic cardiomyopathy (20%)
more
Head And Neck Face:
triangular face
prognathism
biparietal bossing

Genitourinary Kidneys:
unilateral renal agenesis

Neurologic Central Nervous System:
mental retardation, mild

Skin Nails Hair Skin:
cafe-au-lait spots
1-5mm dark lentigines (especially neck and trunk)
lentigines may be absent
lentigines may be congenital or develop in first months to years of life
cafe-noir spots (trunk)

Genitourinary Internal Genitalia Female:
absent ovary
hypoplastic ovary

Head And Neck Ears:
low-set ears
posteriorly rotated ears
sensorineural hearing loss
prominent ears

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum
pectus carinatum
winged scapulae
absent ribs

Endocrine Features:
delayed puberty
late menarche

Skeletal Limbs:
cubitus valgus
limited elbow mobility

Skeletal Spine:
spina bifida occulta
kyphoscoliosis

Head And Neck Nose:
hyposmia
broad, flat nose

Growth Other:
growth retardation

Genitourinary External Genitalia Male:
small penis
hypospadias (50%)

GenitourinaryInternal GenitaliaMale:
cryptorchidism (unilateral or bilateral)


Clinical features from OMIM:

151100

Human phenotypes related to Leopard Syndrome 1:

32 (show all 41)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 low-set ears 32 HP:0000369
3 short neck 32 HP:0000470
4 pectus excavatum 32 HP:0000767
5 ptosis 32 HP:0000508
6 mandibular prognathia 32 HP:0000303
7 pectus carinatum 32 HP:0000768
8 sensorineural hearing impairment 32 HP:0000407
9 short stature 32 HP:0004322
10 delayed puberty 32 HP:0000823
11 intellectual disability, mild 32 HP:0001256
12 hypertrophic cardiomyopathy 32 very rare (1%) HP:0001639
13 cleft palate 32 HP:0000175
14 strabismus 32 HP:0000486
15 epicanthus 32 HP:0000286
16 cryptorchidism 32 HP:0000028
17 cubitus valgus 32 HP:0002967
18 webbed neck 32 HP:0000465
19 scapular winging 32 HP:0003691
20 protruding ear 32 HP:0000411
21 third degree atrioventricular block 32 HP:0001709
22 depressed nasal ridge 32 HP:0000457
23 hypospadias 32 HP:0000047
24 bundle branch block 32 HP:0011710
25 limited elbow movement 32 HP:0002996
26 pulmonic stenosis 32 very rare (1%) HP:0001642
27 spina bifida occulta 32 HP:0003298
28 triangular face 32 HP:0000325
29 multiple lentigines 32 HP:0001003
30 missing ribs 32 HP:0000921
31 hyposmia 32 HP:0004409
32 micropenis 32 HP:0000054
33 kyphoscoliosis 32 HP:0002751
34 unilateral renal agenesis 32 HP:0000122
35 hypoplasia of the ovary 32 HP:0008724
36 cafe-au-lait spot 32 HP:0000957
37 posteriorly rotated ears 32 HP:0000358
38 aplasia of the ovary 32 HP:0010463
39 delayed menarche 32 HP:0012569
40 parietal bossing 32 HP:0000242
41 subvalvular aortic stenosis 32 HP:0001682

UMLS symptoms related to Leopard Syndrome 1:


hyposmia
Sources

Drugs & Therapeutics for Leopard Syndrome 1

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Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Hormonal Sensitivity in Patients With Noonan and LEOPARD Syndromes Unknown status NCT02486731

Search NIH Clinical Center for Leopard Syndrome 1

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Genetic Tests for Leopard Syndrome 1

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Genetic tests related to Leopard Syndrome 1:

# Genetic test Affiliating Genes
1 Leopard Syndrome 1 29 PTPN11
2 Multiple Lentigines 29
Sources

Anatomical Context for Leopard Syndrome 1

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MalaCards organs/tissues related to Leopard Syndrome 1:

41
Ovary, Heart
Sources

Publications for Leopard Syndrome 1

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Articles related to Leopard Syndrome 1:

(show all 32)
# Title Authors Year
1
Multiple Lentigines Arising in Sites of Resolving Psoriatic Plaques after Treatment with Ustekinumab. ( 29853759 )
2018
2
Multiple lentigines arising on resolving psoriatic plaques after treatment with apremilast. ( 29926507 )
2018
3
Noonan syndrome with multiple lentigines and associated craniosynostosis. ( 29356064 )
2018
4
Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy. ( 29717636 )
2018
5
A Novel De novo Mutation of the SASH1 Gene in a Chinese Family with Multiple Lentigines. ( 27840890 )
2017
6
In vivo efficacy of the AKT inhibitor ARQ 092 in Noonan Syndrome with multiple lentigines-associated hypertrophic cardiomyopathy. ( 28582432 )
2017
7
Heterozygous deletion of AKT1 rescues cardiac contractility, but not hypertrophy, in a mouse model of Noonan Syndrome with Multiple Lentigines. ( 28911943 )
2017
8
Noonan syndrome with multiple lentigines with PTPN11 (T468M) gene mutation accompanied with solitary granular cell tumor. ( 28681392 )
2017
9
Urticaria Pigmentosa Mimicking Multiple Lentigine-like Brownish Macules in a 22-Month-Old Boy. ( 28480643 )
2017
10
Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11. ( 28483241 )
2017
11
Multiple giant cell lesions in a patient with Noonan syndrome with multiple lentigines. ( 27238887 )
2016
12
Developmental SHP2 dysfunction underlies cardiac hypertrophy in Noonan syndrome with multiple lentigines. ( 27348588 )
2016
13
Hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26952712 )
2016
14
Elevated calcium transients and increased myofibrillar power generation cause cardiac hypercontractility in a model of Noonan Syndrome with Multiple Lentigines. ( 25724491 )
2015
15
Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with multiple lentigines. ( 26337637 )
2015
16
Rapidly progressive hypertrophic cardiomyopathy in an infant with Noonan syndrome with multiple lentigines: Palliative treatment with a rapamycin analog. ( 25708222 )
2015
17
Pathogenesis of Multiple Lentigines in LEOPARD Syndrome with PTPN11 Gene Mutation. ( 25917897 )
2015
18
Multiple lentigines confined to psoriatic plaques induced by biologic agents in psoriasis therapy: a case and review of the literature. ( 25806714 )
2015
19
A novel heterozygous MAP2K1 mutation in a patient with Noonan syndrome with multiple lentigines. ( 25423878 )
2015
20
Calcified aorto-right ventricular tunnel in a patient with multiple lentigines syndrome. ( 23287380 )
2013
21
Extensive abdominal lipomatosis in a patient with Noonan/LEOPARD syndrome (Noonan syndrome-Multiple Lentigines). ( 22528600 )
2012
22
Familial cases of atypical clinical features genetically diagnosed as LEOPARD syndrome (multiple lentigines syndrome). ( 20883402 )
2010
23
A novel PTPN11 gene mutation bridges Noonan syndrome, multiple lentigines/LEOPARD syndrome and Noonan-like/multiple giant cell lesion syndrome. ( 15470362 )
2004
24
Clinical and molecular analysis of 30 patients with multiple lentigines LEOPARD syndrome. ( 15121796 )
2004
25
Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene. ( 12058348 )
2002
26
Multiple lentigines and testicular microlithiasis. ( 11167985 )
2000
27
Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis). ( 9222968 )
1997
28
Pigmentary anomalies in the multiple lentigines syndrome: Is it distinct from LEOPARD syndrome? ( 9122064 )
1996
29
Multiple lentigines (Leopard) syndrome with Chiara I malformation. ( 7560446 )
1995
30
Noonan syndrome with cafAc-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus. ( 7586657 )
1995
31
Factitial dermatitis as the presenting sign of multiple lentigines syndrome. Therapeutic effect of autodermabrasion. ( 7065683 )
1982
32
Multiple lentigines syndrome: new findings of hypogonadotrophism, hyposmia, and unilateral renal agenesis. ( 5577185 )
1971
Sources

Variations for Leopard Syndrome 1

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UniProtKB/Swiss-Prot genetic disease variations for Leopard Syndrome 1:

75
# Symbol AA change Variation ID SNP ID
1 PTPN11 p.Tyr279Cys VAR_015614 rs121918456
2 PTPN11 p.Thr472Met VAR_015621 rs121918457
3 PTPN11 p.Tyr279Ser VAR_027188 rs121918456
4 PTPN11 p.Ala465Thr VAR_027190 rs121918468
5 PTPN11 p.Gly468Ala VAR_027191 rs121918469
6 PTPN11 p.Arg502Leu VAR_027192 rs397507542
7 PTPN11 p.Arg502Trp VAR_027193 rs397507541
8 PTPN11 p.Gln510Pro VAR_027194 rs397509345
9 PTPN11 p.Gln514Pro VAR_027196 rs121918470
10 PTPN11 p.Gln514Glu VAR_076499 rs397507549

ClinVar genetic disease variations for Leopard Syndrome 1:

6
(show top 50) (show all 52)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTPN11 NM_002834.4(PTPN11): c.214G> T (p.Ala72Ser) single nucleotide variant Pathogenic rs121918453 GRCh37 Chromosome 12, 112888198: 112888198
2 PTPN11 NM_002834.4(PTPN11): c.214G> T (p.Ala72Ser) single nucleotide variant Pathogenic rs121918453 GRCh38 Chromosome 12, 112450394: 112450394
3 PTPN11 NM_002834.4(PTPN11): c.215C> G (p.Ala72Gly) single nucleotide variant Pathogenic rs121918454 GRCh37 Chromosome 12, 112888199: 112888199
4 PTPN11 NM_002834.4(PTPN11): c.215C> G (p.Ala72Gly) single nucleotide variant Pathogenic rs121918454 GRCh38 Chromosome 12, 112450395: 112450395
5 PTPN11 NM_002834.4(PTPN11): c.922A> G (p.Asn308Asp) single nucleotide variant Pathogenic rs28933386 GRCh37 Chromosome 12, 112915523: 112915523
6 PTPN11 NM_002834.4(PTPN11): c.922A> G (p.Asn308Asp) single nucleotide variant Pathogenic rs28933386 GRCh38 Chromosome 12, 112477719: 112477719
7 PTPN11 NM_002834.4(PTPN11): c.923A> G (p.Asn308Ser) single nucleotide variant Pathogenic rs121918455 GRCh37 Chromosome 12, 112915524: 112915524
8 PTPN11 NM_002834.4(PTPN11): c.923A> G (p.Asn308Ser) single nucleotide variant Pathogenic rs121918455 GRCh38 Chromosome 12, 112477720: 112477720
9 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827
10 PTPN11 NM_002834.4(PTPN11): c.836A> G (p.Tyr279Cys) single nucleotide variant Pathogenic/Likely pathogenic rs121918456 GRCh38 Chromosome 12, 112473023: 112473023
11 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh37 Chromosome 12, 112926270: 112926270
12 PTPN11 NM_002834.4(PTPN11): c.1403C> T (p.Thr468Met) single nucleotide variant Pathogenic rs121918457 GRCh38 Chromosome 12, 112488466: 112488466
13 PTPN11 NM_002834.4(PTPN11): c.188A> G (p.Tyr63Cys) single nucleotide variant Pathogenic rs121918459 GRCh37 Chromosome 12, 112888172: 112888172
14 PTPN11 NM_002834.4(PTPN11): c.188A> G (p.Tyr63Cys) single nucleotide variant Pathogenic rs121918459 GRCh38 Chromosome 12, 112450368: 112450368
15 PTPN11 NM_002834.4(PTPN11): c.218C> T (p.Thr73Ile) single nucleotide variant Pathogenic rs121918462 GRCh37 Chromosome 12, 112888202: 112888202
16 PTPN11 NM_002834.4(PTPN11): c.218C> T (p.Thr73Ile) single nucleotide variant Pathogenic rs121918462 GRCh38 Chromosome 12, 112450398: 112450398
17 PTPN11 NM_002834.4(PTPN11): c.236A> G (p.Gln79Arg) single nucleotide variant Pathogenic rs121918466 GRCh37 Chromosome 12, 112888220: 112888220
18 PTPN11 NM_002834.4(PTPN11): c.236A> G (p.Gln79Arg) single nucleotide variant Pathogenic rs121918466 GRCh38 Chromosome 12, 112450416: 112450416
19 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh37 Chromosome 12, 112926248: 112926248
20 PTPN11 NM_002834.4(PTPN11): c.1381G> A (p.Ala461Thr) single nucleotide variant Pathogenic rs121918468 GRCh38 Chromosome 12, 112488444: 112488444
21 PTPN11 NM_002834.4(PTPN11): c.1391G> C (p.Gly464Ala) single nucleotide variant Pathogenic rs121918469 GRCh37 Chromosome 12, 112926258: 112926258
22 PTPN11 NM_002834.4(PTPN11): c.1391G> C (p.Gly464Ala) single nucleotide variant Pathogenic rs121918469 GRCh38 Chromosome 12, 112488454: 112488454
23 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh37 Chromosome 12, 112926909: 112926909
24 PTPN11 NM_002834.4(PTPN11): c.1529A> C (p.Gln510Pro) single nucleotide variant Pathogenic rs121918470 GRCh38 Chromosome 12, 112489105: 112489105
25 PTPN11 NM_002834.4(PTPN11): c.174C> G (p.Asn58Lys) single nucleotide variant Pathogenic/Likely pathogenic rs397507506 GRCh37 Chromosome 12, 112888158: 112888158
26 PTPN11 NM_002834.4(PTPN11): c.174C> G (p.Asn58Lys) single nucleotide variant Pathogenic/Likely pathogenic rs397507506 GRCh38 Chromosome 12, 112450354: 112450354
27 PTPN11 NM_002834.4(PTPN11): c.181G> A (p.Asp61Asn) single nucleotide variant Pathogenic rs397507510 GRCh37 Chromosome 12, 112888165: 112888165
28 PTPN11 NM_002834.4(PTPN11): c.181G> A (p.Asp61Asn) single nucleotide variant Pathogenic rs397507510 GRCh38 Chromosome 12, 112450361: 112450361
29 PTPN11 NM_002834.4(PTPN11): c.417G> C (p.Glu139Asp) single nucleotide variant Pathogenic rs397507520 GRCh37 Chromosome 12, 112891083: 112891083
30 PTPN11 NM_002834.4(PTPN11): c.417G> C (p.Glu139Asp) single nucleotide variant Pathogenic rs397507520 GRCh38 Chromosome 12, 112453279: 112453279
31 PTPN11 NM_002834.4(PTPN11): c.1492C> T (p.Arg498Trp) single nucleotide variant Pathogenic rs397507541 GRCh37 Chromosome 12, 112926872: 112926872
32 PTPN11 NM_002834.4(PTPN11): c.1492C> T (p.Arg498Trp) single nucleotide variant Pathogenic rs397507541 GRCh38 Chromosome 12, 112489068: 112489068
33 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh37 Chromosome 12, 112926873: 112926873
34 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh38 Chromosome 12, 112489069: 112489069
35 PTPN11 NM_002834.4(PTPN11): c.1507G> C (p.Gly503Arg) single nucleotide variant Pathogenic rs397507545 GRCh37 Chromosome 12, 112926887: 112926887
36 PTPN11 NM_002834.4(PTPN11): c.1507G> C (p.Gly503Arg) single nucleotide variant Pathogenic rs397507545 GRCh38 Chromosome 12, 112489083: 112489083
37 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh37 Chromosome 12, 112926897: 112926897
38 PTPN11 NM_002834.4(PTPN11): c.1517A> C (p.Gln506Pro) single nucleotide variant Pathogenic rs397507548 GRCh38 Chromosome 12, 112489093: 112489093
39 PTPN11 NM_002834.4(PTPN11): c.1528C> G (p.Gln510Glu) single nucleotide variant Pathogenic rs397507549 GRCh37 Chromosome 12, 112926908: 112926908
40 PTPN11 NM_002834.4(PTPN11): c.1528C> G (p.Gln510Glu) single nucleotide variant Pathogenic rs397507549 GRCh38 Chromosome 12, 112489104: 112489104
41 PTPN11 NM_002834.4(PTPN11): c.1530G> C (p.Gln510His) single nucleotide variant Pathogenic rs397507550 GRCh37 Chromosome 12, 112926910: 112926910
42 PTPN11 NM_002834.4(PTPN11): c.1530G> C (p.Gln510His) single nucleotide variant Pathogenic rs397507550 GRCh38 Chromosome 12, 112489106: 112489106
43 PTPN11 NM_002834.4(PTPN11): c.836A> C (p.Tyr279Ser) single nucleotide variant Pathogenic rs121918456 GRCh37 Chromosome 12, 112910827: 112910827
44 PTPN11 NM_002834.4(PTPN11): c.836A> C (p.Tyr279Ser) single nucleotide variant Pathogenic rs121918456 GRCh38 Chromosome 12, 112473023: 112473023
45 PTPN11 NM_002834.4(PTPN11): c.1682C> T (p.Pro561Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs141140214 GRCh37 Chromosome 12, 112940030: 112940030
46 PTPN11 NM_002834.4(PTPN11): c.1682C> T (p.Pro561Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs141140214 GRCh38 Chromosome 12, 112502226: 112502226
47 PTPN11 NM_002834.4(PTPN11): c.473G> C (p.Gly158Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 12, 112891139: 112891139
48 PTPN11 NM_002834.4(PTPN11): c.473G> C (p.Gly158Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 12, 112453335: 112453335
49 PTPN11 NM_002834.4(PTPN11): c.1579C> T (p.Arg527Cys) single nucleotide variant Uncertain significance rs191525506 GRCh37 Chromosome 12, 112926959: 112926959
50 PTPN11 NM_002834.4(PTPN11): c.1579C> T (p.Arg527Cys) single nucleotide variant Uncertain significance rs191525506 GRCh38 Chromosome 12, 112489155: 112489155
Sources

Expression for Leopard Syndrome 1

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Search GEO for disease gene expression data for Leopard Syndrome 1.
Sources

Pathways for Leopard Syndrome 1

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Sources

GO Terms for Leopard Syndrome 1

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Sources

Sources for Leopard Syndrome 1

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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
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
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
73 UMLS
74 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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