MCID: LGS001
MIFTS: 50

Legius Syndrome

Categories: Genetic diseases, Rare diseases, Skin diseases, Fetal diseases, Neuronal diseases

Aliases & Classifications for Legius Syndrome

MalaCards integrated aliases for Legius Syndrome:

Name: Legius Syndrome 57 24 53 25 59 75 37 29 13 6 40
Neurofibromatosis Type 1-Like Syndrome 57 24 25
Nfls 57 25 75
Neurofibromatosis 1-Like Syndrome 59 75
Neurofibromatosis Type 1-Like Syndrome; Nfls 57
Neurofibromatosis, Type 1-Like Syndrome 73
Neurofibromatosis Type 1 Like Syndrome 53
Cafe-Au-Lait Spots 44
Nf1-Like Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
legius syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
some patients do not have dysmorphic features
phenotypic overlap with neurofibromatosis 1 (nf1, )


HPO:

32
legius syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The vast majority of individuals with spred1 pathogenic variants have café au lait macules and/or freckling; however, the age of pigment penetrance is not established. only two individuals (a 60-year-old male and a 2-year-old child), each with a presumed spred1 pathogenic variant, were reported not to have café au lait macules or freckling [brems et al 2007, messiaen et al 2009]...

Classifications:



External Ids:

OMIM 57 611431
Orphanet 59 ORPHA137605
MESH via Orphanet 45 C548032
UMLS via Orphanet 74 C1969623
ICD10 via Orphanet 34 Q85.0
MedGen 42 C1969623
MeSH 44 D019080
KEGG 37 H01986
UMLS 73 C1969623

Summaries for Legius Syndrome

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 137605Disease definitionLegius syndrome, also known as NF1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.EpidemiologyThe prevalence of Legius syndrome is not known. Fewer than 200 cases have been reported to date. Prevalence may be higher than expected due to misdiagnosis of cases as neurofibromatosis type 1 (NF1, see this term). The incidence of NF1 is reported to be 1/3000, and about 2% of patients fulfilling diagnostic criteria for NF1 are found to have the genetic mutation underlying Legius syndrome (SPRED1).Clinical descriptionThe clinical presentation of Legius syndrome is very similar to that of NF1. Patients typically present with multiple café-au-lait spots sometimes associated with intertriginous freckling, but lack Lisch nodules, optic pathway gliomas, bone abnormalities, neurofibromas or other tumor manifestations. The number of café-au-lait macules tends to increase with age during childhood. Other less common manifestations include short stature, macrocephaly, Noonan-like facies, pectus excavatum/carinatum, lipomas, hypopigmented macules, vascular lesions, learning disabilities, attention deficit/hyperactivity disorder (ADHD), and developmental delay.EtiologyLegius syndrome is caused by heterozygous inactivating mutations in the SPRED1 gene (15q14), involved in regulation of the RAS-MAPK signal transduction pathway. Nearly 100 different mutations in this gene have been identified. The proportion of cases related to de novo mutations is not yet known. No genotype-phenotype correlations have been found.Diagnostic methodsAbout 50% of patients with Legius syndrome fulfill the diagnostic criteria for NF1, but they have a far milder phenotype compared to NF1 patients. Diagnosis based solely on the presence of clinical features is difficult, given the overlap with other disorders characterized by multiple café-au-lait spots. The presence of characteristic clinical signs in parents of affected individuals is supportive of diagnosis. However, molecular genetic testing is required to confirm the diagnosis and testing is available on a clinical basis.Differential diagnosisLegius syndrome is differentiated from NF1 by the absence of the non-pigmentary clinical manifestations seen in this disorder (i.e. Lisch nodules, neurofibromas, optic glioma, bone abnormalities). Correct diagnosis is essential because of the differences in prognosis and long-term monitoring between Legius syndrome and NF1. Other disorders to consider include Noonan syndrome, Noonan syndrome with lentigines (LEOPARD syndrome), and McCune-Albright syndrome (see these terms).Antenatal diagnosisPrenatal diagnosis is possible and requires prior identification of the disease-causing mutation in the family.Genetic counselingLegius syndrome follows an autosomal dominant pattern of inheritance. Genetic counseling should be provided to affected families.Management and treatmentDrug therapy should be considered for the behavioral manifestations of the disorder (ADHD). Physical, speech, and occupational therapy is recommended for those with developmental delay and educational support for those with learning difficulties.PrognosisGiven the current knowledge of disease manifestations and complications, the prognosis for patients with Legius syndrome is considered to be very good.Visit the Orphanet disease page for more resources.

MalaCards based summary : Legius Syndrome, also known as neurofibromatosis type 1-like syndrome, is related to noonan syndrome 1 and neurofibromatosis, type iv, of riccardi. An important gene associated with Legius Syndrome is SPRED1 (Sprouty Related EVH1 Domain Containing 1), and among its related pathways/superpathways are Cytokine Signaling in Immune system and Negative regulation of FGFR3 signaling. Affiliated tissues include skin, testes and bone, and related phenotypes are high palate and macrocephaly

Genetics Home Reference : 25 Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals.

OMIM : 57 Legius syndrome is an autosomal dominant disorder that shows some similarities to neurofibromatosis type I (NF1; 162200), which is caused by mutation in the neurofibromin gene (613113); however, Legius syndrome is less severe. Individuals with Legius syndrome typically have multiple cafe-au-lait spots, sometimes associated with skin fold freckling, variable dysmorphic features such as hypertelorism or macrocephaly, lipomas, and mild learning disabilities or attention problems. Legius syndrome is not associated with neurofibromas, optic gliomas, Lisch nodules, or tumor predisposition. The SPRED1 gene encodes a negative regulator of the RAS-MAPK pathway, similar to neurofibromin, and thus may be considered a RASopathy (review by Brems et al., 2012). (611431)

UniProtKB/Swiss-Prot : 75 Neurofibromatosis 1-like syndrome: A disorder characterized mainly by cafe au lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1, axillary freckling, and macrocephaly. Additional clinical manifestations include Noonan-like facial dysmorphism, lipomas, learning disabilities and attention deficit-hyperactivity.

Wikipedia : 76 Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was... more...

GeneReviews: NBK47312

Related Diseases for Legius Syndrome

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

(show all 50)
# Related Disease Score Top Affiliating Genes
1 noonan syndrome 1 31.3 NF1 PTPN11 SPRED1
2 neurofibromatosis, type iv, of riccardi 29.2 MSH6 NF1 PTPN11
3 cafe-au-lait spots, multiple 12.8
4 watson syndrome 12.4
5 neurofibromatosis, type i 11.3
6 plexiform neurofibroma 10.6 NF1 SPRED1
7 neurilemmomatosis 10.5 NF1 SPRED1
8 adrenal cortical adenocarcinoma 10.5 SPRY1 SPRY2
9 pulmonary valve disease 10.2 PTPN11 SPRED1
10 neurofibromatosis-noonan syndrome 10.2 NF1 PTPN11
11 myelodysplastic myeloproliferative cancer 10.2 NF1 PTPN11
12 leopard syndrome 10.1 NF1 PTPN11
13 deafness, autosomal recessive 26 10.1 PTPN11 SPRY2
14 choroiditis 10.0
15 pulmonic stenosis 10.0 NF1 PTPN11
16 amyotrophic lateral sclerosis 1 10.0
17 lateral sclerosis 10.0
18 juvenile myelomonocytic leukemia 9.9 NF1 PTPN11 SPRED1
19 body mass index quantitative trait locus 1 9.9
20 neuronitis 9.9
21 glioblastoma 9.9
22 encephalopathy 9.9
23 appendix carcinoid tumor 9.8 MSH2 MSH6
24 adenosquamous colon carcinoma 9.8 MSH2 MSH6
25 sebaceous adenoma 9.8 MSH2 MSH6
26 hydrocephalus, normal-pressure 9.8
27 charcot-marie-tooth disease 9.8
28 hydrocephalus 9.8
29 tooth disease 9.8
30 substance abuse 9.8
31 retinitis 9.8
32 craniopharyngioma 9.8
33 peripheral nervous system disease 9.8
34 neuropathy 9.8
35 glioma 9.8
36 head injury 9.8
37 subcortical arteriosclerotic encephalopathy 9.8
38 dementia pugilistica 9.8
39 attenuated familial adenomatous polyposis 9.7 MSH2 MSH6
40 lynch syndrome i 9.6 MSH2 MSH6
41 autosomal dominant café au lait spots 9.6 NF1 PTPN11 SPRED1 SPRED2
42 cecum adenocarcinoma 9.6 MSH2 MSH6
43 cardiofaciocutaneous syndrome 1 9.5 PTPN11 SPRED1
44 sebaceous adenocarcinoma 9.5 MSH2 MSH6
45 autosomal genetic disease 9.4 MSH2 MSH6 NF1
46 muir-torre syndrome 9.4 MSH2 MSH6
47 autosomal dominant disease 9.4 MSH2 MSH6 NF1
48 skin benign neoplasm 9.3 MSH2 MSH6
49 mismatch repair cancer syndrome 9.2 MSH2 MSH6
50 rhabdomyosarcoma 8.8 MSH2 MSH6 PTPN11

Graphical network of the top 20 diseases related to Legius Syndrome:



Diseases related to Legius Syndrome

Symptoms & Phenotypes for Legius Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
ptosis
downslanting palpebral fissures
epicanthal folds

Skin Nails Hair Hair:
low posterior hairline

Neurologic Central Nervous System:
no neurofibromas
learning difficulties

Head And Neck Ears:
low-set posteriorly rotated ears

Chest Ribs Sternum Clavicles And Scapulae:
pectus deformities (in some patients)

Head And Neck Face:
noonan-like facies in a minority of patients
triangular face with age

Head And Neck Mouth:
short neck
micrognathia
high arched palate
deeply grooved philtrum
high peaks of upper lip vermilion border

Muscle Soft Tissue:
hypotonia
lipomas

Skin Nails Hair Skin:
cafe-au-lait spots
axillary freckling

Neurologic Behavioral Psychiatric Manifestations:
attention deficit-hyperactivity

Head And Neck Head:
macrocephaly (less common)


Clinical features from OMIM:

611431

Human phenotypes related to Legius Syndrome:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 macrocephaly 32 HP:0000256
3 epicanthus 32 HP:0000286
4 hypertelorism 32 HP:0000316
5 triangular face 32 HP:0000325
6 micrognathia 32 HP:0000347
7 low-set, posteriorly rotated ears 32 HP:0000368
8 short neck 32 HP:0000470
9 downslanted palpebral fissures 32 HP:0000494
10 ptosis 32 HP:0000508
11 abnormality of the sternum 32 occasional (7.5%) HP:0000766
12 cafe-au-lait spot 32 HP:0000957
13 axillary freckling 32 HP:0000997
14 multiple lipomas 32 HP:0001012
15 neurofibromas 32 HP:0001067
16 generalized hypotonia 32 HP:0001290
17 specific learning disability 32 HP:0001328
18 low posterior hairline 32 HP:0002162
19 high, narrow palate 32 HP:0002705
20 attention deficit hyperactivity disorder 32 HP:0007018

MGI Mouse Phenotypes related to Legius Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.55 SPRY2 SPRY4 NF1 PTPN11 SPRED1
2 limbs/digits/tail MP:0005371 9.43 NF1 PTPN11 SPRED1 SPRED2 SPRY2 SPRY4
3 neoplasm MP:0002006 9.1 MSH2 MSH6 NF1 PTPN11 SPRY1 SPRY2

Drugs & Therapeutics for Legius Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Disease Severity in Adults With Neurofibromatosis Type 1 (NF1) Active, not recruiting NCT00111384

Search NIH Clinical Center for Legius Syndrome

Cochrane evidence based reviews: cafe-au-lait spots

Genetic Tests for Legius Syndrome

Genetic tests related to Legius Syndrome:

# Genetic test Affiliating Genes
1 Legius Syndrome 29 SPRED1

Anatomical Context for Legius Syndrome

MalaCards organs/tissues related to Legius Syndrome:

41
Skin, Testes, Bone

Publications for Legius Syndrome

Articles related to Legius Syndrome:

(show all 25)
# Title Authors Year
1
Correction: The absence that makes the difference: choroidal abnormalities in Legius syndrome. ( 29479078 )
2018
2
Legius syndrome: A case report. ( 28378438 )
2017
3
The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation. ( 28150585 )
2017
4
The absence that makes the difference: choroidal abnormalities in Legius syndrome. ( 28747691 )
2017
5
Interaction between a Domain of the Negative Regulator of the Ras-ERK Pathway, SPRED1 Protein, and the GTPase-activating Protein-related Domain of Neurofibromin Is Implicated in Legius Syndrome and Neurofibromatosis Type 1. ( 26635368 )
2016
6
Legius syndrome: case report and review of literature. ( 25883013 )
2015
7
Legius Syndrome: two novel mutations in the SPRED1 gene. ( 27081556 )
2015
8
Family with Legius syndrome (neurofibromatosis type 1-like syndrome). ( 25981987 )
2015
9
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. ( 24469042 )
2014
10
Legius Syndrome, an Update.Molecular Pathology of Mutations in SPRED1. ( 24334617 )
2013
11
CafAc-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome. ( 22438235 )
2012
12
Review and update of SPRED1 mutations causing Legius syndrome. ( 22753041 )
2012
13
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. ( 22751498 )
2012
14
Identification of five novel SPRED1 germline mutations in Legius syndrome. ( 21649642 )
2011
15
Observations on intelligence and behavior in 15 patients with Legius syndrome. ( 21495177 )
2011
16
Legius syndrome in fourteen families. ( 21089071 )
2011
17
The SPRED1 Variants Repository for Legius Syndrome. ( 22384355 )
2011
18
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108420 )
2010
19
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108386 )
2010
20
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108385 )
2010
21
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108421 )
2010
22
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108422 )
2010
23
Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. ( 19920242 )
2009
24
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. ( 19443465 )
2009
25
Legius Syndrome ( 20945555 )
1993

Variations for Legius Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Legius Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 SPRED1 p.Trp31Cys VAR_064827
2 SPRED1 p.Val44Asp VAR_064828 rs121434318

ClinVar genetic disease variations for Legius Syndrome:

6
(show top 50) (show all 282)
# Gene Variation Type Significance SNP ID Assembly Location
1 SPRED1 NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter) single nucleotide variant Pathogenic rs121434315 GRCh37 Chromosome 15, 38591731: 38591731
2 SPRED1 NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter) single nucleotide variant Pathogenic rs121434315 GRCh38 Chromosome 15, 38299530: 38299530
3 SPRED1 NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter) single nucleotide variant Pathogenic rs121434316 GRCh37 Chromosome 15, 38641677: 38641677
4 SPRED1 NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter) single nucleotide variant Pathogenic rs121434312 GRCh37 Chromosome 15, 38614583: 38614583
5 SPRED1 NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter) single nucleotide variant Pathogenic rs121434312 GRCh38 Chromosome 15, 38322382: 38322382
6 SPRED1 NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic rs121434313 GRCh37 Chromosome 15, 38591611: 38591611
7 SPRED1 NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic rs121434313 GRCh38 Chromosome 15, 38299410: 38299410
8 SPRED1 SPRED1, IVS5DS, G-A, +1 single nucleotide variant Pathogenic
9 SPRED1 NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter) single nucleotide variant Pathogenic rs121434314 GRCh37 Chromosome 15, 38641683: 38641683
10 SPRED1 NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter) single nucleotide variant Pathogenic rs121434314 GRCh38 Chromosome 15, 38349482: 38349482
11 SPRED1 NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter) single nucleotide variant Pathogenic rs121434316 GRCh38 Chromosome 15, 38349476: 38349476
12 SPRED1 NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter) single nucleotide variant Pathogenic rs121434317 GRCh37 Chromosome 15, 38643314: 38643314
13 SPRED1 NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter) single nucleotide variant Pathogenic rs121434317 GRCh38 Chromosome 15, 38351113: 38351113
14 SPRED1 NM_152594.2(SPRED1): c.131T> A (p.Val44Asp) single nucleotide variant Pathogenic rs121434318 GRCh37 Chromosome 15, 38591672: 38591672
15 SPRED1 NM_152594.2(SPRED1): c.131T> A (p.Val44Asp) single nucleotide variant Pathogenic rs121434318 GRCh38 Chromosome 15, 38299471: 38299471
16 SPRED1 SPRED1, 2-BP DEL, 1045AG deletion Pathogenic
17 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh37 Chromosome 12, 112926873: 112926873
18 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh38 Chromosome 12, 112489069: 112489069
19 SPRED1 NM_152594.2(SPRED1): c.702C> G (p.Ile234Met) single nucleotide variant Conflicting interpretations of pathogenicity rs138553244 GRCh37 Chromosome 15, 38643232: 38643232
20 SPRED1 NM_152594.2(SPRED1): c.702C> G (p.Ile234Met) single nucleotide variant Conflicting interpretations of pathogenicity rs138553244 GRCh38 Chromosome 15, 38351031: 38351031
21 SPRED1 NM_152594.2(SPRED1): c.926T> C (p.Val309Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs114636635 GRCh37 Chromosome 15, 38643456: 38643456
22 SPRED1 NM_152594.2(SPRED1): c.926T> C (p.Val309Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs114636635 GRCh38 Chromosome 15, 38351255: 38351255
23 NF1 NM_001042492.2(NF1): c.1987G> A (p.Gly663Arg) single nucleotide variant Uncertain significance rs140653372 GRCh37 Chromosome 17, 29552254: 29552254
24 NF1 NM_001042492.2(NF1): c.1987G> A (p.Gly663Arg) single nucleotide variant Uncertain significance rs140653372 GRCh38 Chromosome 17, 31225236: 31225236
25 NF1 NM_000267.3(NF1): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs768638173 GRCh38 Chromosome 17, 31226474: 31226474
26 NF1 NM_000267.3(NF1): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs768638173 GRCh37 Chromosome 17, 29553492: 29553492
27 NF1 NM_000267.3(NF1): c.7419G> A (p.Trp2473Ter) single nucleotide variant Pathogenic rs863224493 GRCh37 Chromosome 17, 29679299: 29679299
28 NF1 NM_000267.3(NF1): c.7419G> A (p.Trp2473Ter) single nucleotide variant Pathogenic rs863224493 GRCh38 Chromosome 17, 31352281: 31352281
29 SPRED1 NM_152594.2(SPRED1): c.51G> A (p.Val17=) single nucleotide variant Likely benign rs864622421 GRCh38 Chromosome 15, 38299391: 38299391
30 SPRED1 NM_152594.2(SPRED1): c.51G> A (p.Val17=) single nucleotide variant Likely benign rs864622421 GRCh37 Chromosome 15, 38591592: 38591592
31 SPRED1 NM_152594.2(SPRED1): c.796_797delAT (p.Met266Valfs) deletion Pathogenic rs864622410 GRCh37 Chromosome 15, 38643326: 38643327
32 SPRED1 NM_152594.2(SPRED1): c.796_797delAT (p.Met266Valfs) deletion Pathogenic rs864622410 GRCh38 Chromosome 15, 38351125: 38351126
33 SPRED1 NM_152594.2(SPRED1): c.587C> T (p.Thr196Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs147474792 GRCh38 Chromosome 15, 38349426: 38349426
34 SPRED1 NM_152594.2(SPRED1): c.587C> T (p.Thr196Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs147474792 GRCh37 Chromosome 15, 38641627: 38641627
35 SPRED1 NM_152594.2(SPRED1): c.685-8T> C single nucleotide variant Likely benign rs760690837 GRCh37 Chromosome 15, 38643207: 38643207
36 SPRED1 NM_152594.2(SPRED1): c.685-8T> C single nucleotide variant Likely benign rs760690837 GRCh38 Chromosome 15, 38351006: 38351006
37 SPRED1 NM_152594.2(SPRED1): c.886T> C (p.Cys296Arg) single nucleotide variant Likely benign rs554327738 GRCh37 Chromosome 15, 38643416: 38643416
38 SPRED1 NM_152594.2(SPRED1): c.886T> C (p.Cys296Arg) single nucleotide variant Likely benign rs554327738 GRCh38 Chromosome 15, 38351215: 38351215
39 SPRED1 NM_152594.2(SPRED1): c.939G> A (p.Thr313=) single nucleotide variant Benign/Likely benign rs140644874 GRCh37 Chromosome 15, 38643469: 38643469
40 SPRED1 NM_152594.2(SPRED1): c.939G> A (p.Thr313=) single nucleotide variant Benign/Likely benign rs140644874 GRCh38 Chromosome 15, 38351268: 38351268
41 SPRED1 NM_152594.2(SPRED1): c.995G> A (p.Arg332His) single nucleotide variant Uncertain significance rs779966392 GRCh37 Chromosome 15, 38643525: 38643525
42 SPRED1 NM_152594.2(SPRED1): c.995G> A (p.Arg332His) single nucleotide variant Uncertain significance rs779966392 GRCh38 Chromosome 15, 38351324: 38351324
43 SPRED1 NM_152594.2(SPRED1): c.1005C> T (p.Cys335=) single nucleotide variant Likely benign rs768937237 GRCh38 Chromosome 15, 38351334: 38351334
44 SPRED1 NM_152594.2(SPRED1): c.1005C> T (p.Cys335=) single nucleotide variant Likely benign rs768937237 GRCh37 Chromosome 15, 38643535: 38643535
45 SPRED1 NM_152594.2(SPRED1): c.1151_1152delAG (p.Glu384Glyfs) deletion Pathogenic rs878855228 GRCh37 Chromosome 15, 38643681: 38643682
46 SPRED1 NM_152594.2(SPRED1): c.1151_1152delAG (p.Glu384Glyfs) deletion Pathogenic rs878855228 GRCh38 Chromosome 15, 38351480: 38351481
47 46;XX;t(3;12)(q13.2;q14)dn Translocation Pathogenic
48 46;XY;inv(6)(q22.2q27)dn inversion Pathogenic
49 46;XY;t(4;7)(q31;q22)dn Translocation Uncertain significance
50 46;XX;t(1;2)(q42.3;q24.2)dn Translocation Uncertain significance

Copy number variations for Legius Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 91538 15 31400000 37900000 Copy number SPRED1 Legius syndrome

Expression for Legius Syndrome

Search GEO for disease gene expression data for Legius Syndrome.

Pathways for Legius Syndrome

Pathways related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.96 NF1 PTPN11 SPRED1 SPRED2 SPRED3
2
Show member pathways
12.07 PTPN11 SPRED1 SPRED2 SPRY2
3
Show member pathways
11.79 PTPN11 SPRED1 SPRED2
4
Show member pathways
11.74 PTPN11 SPRED1 SPRED2 SPRY2
5 11.73 MSH2 MSH6 NF1
6 11.67 SPRED1 SPRY1 SPRY2
7
Show member pathways
11.37 NF1 SPRED1 SPRED2 SPRED3
8 11.17 PTPN11 SPRY2
9 11.14 MSH2 MSH6
10 10.98 NF1 PTPN11 SPRY1 SPRY2
11 10.9 MSH2 MSH6

GO Terms for Legius Syndrome

Cellular components related to Legius Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytosol GO:0005829 9.81 MSH6 NF1 PTPN11 SPRED1 SPRED2 SPRY1
2 mismatch repair complex GO:0032300 8.96 MSH2 MSH6
3 MutSalpha complex GO:0032301 8.62 MSH2 MSH6

Biological processes related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.98 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2 SPRY3
2 negative regulation of angiogenesis GO:0016525 9.77 NF1 SPRED1 SPRY2
3 fibroblast growth factor receptor signaling pathway GO:0008543 9.74 PTPN11 SPRED1 SPRED2
4 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.67 SPRED1 SPRY1 SPRY2 SPRY4
5 metanephros development GO:0001656 9.64 NF1 SPRY1
6 mismatch repair GO:0006298 9.63 MSH2 MSH6
7 negative regulation of epidermal growth factor receptor signaling pathway GO:0042059 9.63 SPRY1 SPRY2
8 inactivation of MAPK activity GO:0000188 9.62 SPRED1 SPRED2
9 negative regulation of MAPK cascade GO:0043409 9.62 NF1 SPRED1
10 animal organ development GO:0048513 9.62 SPRY1 SPRY2 SPRY3 SPRY4
11 establishment of mitotic spindle orientation GO:0000132 9.61 SPRY1 SPRY2
12 somatic hypermutation of immunoglobulin genes GO:0016446 9.61 MSH2 MSH6
13 isotype switching GO:0045190 9.6 MSH2 MSH6
14 determination of adult lifespan GO:0008340 9.58 MSH2 MSH6
15 positive regulation of DNA damage response, signal transduction by p53 class mediator GO:0043517 9.58 SPRED1 SPRED2
16 negative regulation of peptidyl-threonine phosphorylation GO:0010801 9.58 SPRED1 SPRED2 SPRY2
17 bud elongation involved in lung branching GO:0060449 9.56 SPRY1 SPRY2
18 negative regulation of fibroblast growth factor receptor signaling pathway GO:0040037 9.56 SPRY1 SPRY2 SPRY3 SPRY4
19 positive regulation of helicase activity GO:0051096 9.55 MSH2 MSH6
20 negative regulation of MAP kinase activity GO:0043407 9.55 NF1 SPRY1 SPRY2 SPRY3 SPRY4
21 negative regulation of DNA recombination GO:0045910 9.54 MSH2 MSH6
22 maintenance of DNA repeat elements GO:0043570 9.52 MSH2 MSH6
23 somatic recombination of immunoglobulin gene segments GO:0016447 9.51 MSH2 MSH6
24 negative regulation of neurotrophin TRK receptor signaling pathway GO:0051387 9.49 SPRY1 SPRY2
25 meiotic mismatch repair GO:0000710 9.48 MSH2 MSH6
26 regulation of protein deacetylation GO:0090311 9.46 SPRED1 SPRED2
27 negative regulation of Ras protein signal transduction GO:0046580 9.35 NF1 SPRY1 SPRY2 SPRY3 SPRY4
28 regulation of signal transduction GO:0009966 9.17 SPRED1 SPRED2 SPRED3 SPRY1 SPRY2 SPRY3

Molecular functions related to Legius Syndrome according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.8 MSH2 SPRED1 SPRED2 SPRY2
2 DNA-dependent ATPase activity GO:0008094 9.52 MSH2 MSH6
3 ADP binding GO:0043531 9.51 MSH2 MSH6
4 four-way junction DNA binding GO:0000400 9.48 MSH2 MSH6
5 mismatched DNA binding GO:0030983 9.46 MSH2 MSH6
6 oxidized purine DNA binding GO:0032357 9.43 MSH2 MSH6
7 MutLalpha complex binding GO:0032405 9.4 MSH2 MSH6
8 guanine/thymine mispair binding GO:0032137 9.37 MSH2 MSH6
9 stem cell factor receptor binding GO:0005173 9.32 SPRED1 SPRED2
10 single guanine insertion binding GO:0032142 9.26 MSH2 MSH6
11 single base insertion or deletion binding GO:0032138 9.16 MSH2 MSH6
12 single thymine insertion binding GO:0032143 8.96 MSH2 MSH6
13 protein serine/threonine kinase inhibitor activity GO:0030291 8.8 SPRED1 SPRED2 SPRY2

Sources for Legius 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
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
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