NFLS
MCID: LGS001
MIFTS: 51

Legius Syndrome (NFLS)

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

Aliases & Classifications for Legius Syndrome

MalaCards integrated aliases for Legius Syndrome:

Name: Legius Syndrome 58 25 54 26 60 76 38 30 13 6 41
Neurofibromatosis Type 1-Like Syndrome 58 25 26
Nfls 58 26 76
Neurofibromatosis 1-Like Syndrome 60 76
Neurofibromatosis Type 1-Like Syndrome; Nfls 58
Neurofibromatosis, Type 1-Like Syndrome 74
Neurofibromatosis Type 1 Like Syndrome 54
Cafe-Au-Lait Spots 45
Nf1-Like Syndrome 60
Lgss 58

Characteristics:

Orphanet epidemiological data:

60
legius syndrome
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide); Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant

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


HPO:

33
legius syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

25
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 58 611431
KEGG 38 H01986
MeSH 45 D019080
MESH via Orphanet 46 C548032
ICD10 via Orphanet 35 Q85.0
UMLS via Orphanet 75 C1969623
Orphanet 60 ORPHA137605
MedGen 43 C1969623
UMLS 74 C1969623

Summaries for Legius Syndrome

NIH Rare Diseases : 54 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 neurofibromatosis, type iv, of riccardi and cafe-au-lait spots, multiple. An important gene associated with Legius Syndrome is SPRED1 (Sprouty Related EVH1 Domain Containing 1), and among its related pathways/superpathways are Kit receptor signaling pathway and Signaling by FGFR2. Affiliated tissues include skin, bone and testes, and related phenotypes are abnormality of the sternum and macrocephaly

Genetics Home Reference : 26 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 : 58 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 : 76 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 : 77 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 top 50) (show all 68)
# Related Disease Score Top Affiliating Genes
1 neurofibromatosis, type iv, of riccardi 30.3 MSH6 NF1 PTPN11
2 cafe-au-lait spots, multiple 12.9
3 watson syndrome 12.6
4 autosomal dominant café au lait spots 12.3
5 gastrocutaneous syndrome 11.9
6 fibromatosis multiple non ossifying 11.7
7 mccune-albright syndrome 11.6
8 mismatch repair cancer syndrome 11.6
9 ring chromosome 15 11.6
10 neurofibromatosis, type i 11.5
11 noonan syndrome 1 11.1
12 moyamoya disease 1 10.5
13 microcephaly 10.5
14 ring chromosome 12 10.5
15 plexiform neurofibroma 10.3 NF1 SPRED1
16 neurilemmomatosis 10.3 NF1 SPRED1
17 adrenal cortical adenocarcinoma 10.2 SPRY1 SPRY2
18 encephalopathy 10.2
19 neurofibromatosis-noonan syndrome 10.2 NF1 PTPN11
20 pulmonary valve disease 10.2 PTPN11 SPRED1
21 amyotrophic lateral sclerosis 1 10.1
22 lateral sclerosis 10.1
23 head injury 10.1
24 myelodysplastic myeloproliferative cancer 10.1 NF1 PTPN11
25 leopard syndrome 10.1 NF1 PTPN11
26 deafness, autosomal recessive 26 10.1 PTPN11 SPRY2
27 piebald trait 10.1
28 body mass index quantitative trait locus 1 10.1
29 brain injury 10.1
30 traumatic brain injury 10.1
31 substance abuse 10.1
32 human immunodeficiency virus infectious disease 10.1
33 glioblastoma 10.1
34 dementia pugilistica 10.1
35 juvenile myelomonocytic leukemia 10.0 NF1 PTPN11 SPRED1
36 pulmonic stenosis 9.9 NF1 PTPN11
37 parkinson disease, late-onset 9.9
38 spondylolisthesis 9.9
39 hydrocephalus, normal-pressure 9.9
40 charcot-marie-tooth disease, axonal, type 2e 9.9
41 charcot-marie-tooth disease, demyelinating, type 1f 9.9
42 neuronopathy, distal hereditary motor, type iib 9.9
43 charcot-marie-tooth disease 9.9
44 hydrocephalus 9.9
45 pre-eclampsia 9.9
46 tooth disease 9.9
47 cystadenoma 9.9
48 glioblastoma multiforme 9.9
49 craniopharyngioma 9.9
50 peripheral nervous system disease 9.9

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



Diseases related to Legius Syndrome

Symptoms & Phenotypes for Legius Syndrome

Human phenotypes related to Legius Syndrome:

33 (show all 20)
# Description HPO Frequency HPO Source Accession
1 abnormality of the sternum 33 occasional (7.5%) HP:0000766
2 macrocephaly 33 HP:0000256
3 hypertelorism 33 HP:0000316
4 short neck 33 HP:0000470
5 high palate 33 HP:0000218
6 ptosis 33 HP:0000508
7 micrognathia 33 HP:0000347
8 epicanthus 33 HP:0000286
9 attention deficit hyperactivity disorder 33 HP:0007018
10 specific learning disability 33 HP:0001328
11 low posterior hairline 33 HP:0002162
12 high, narrow palate 33 HP:0002705
13 multiple lipomas 33 HP:0001012
14 low-set, posteriorly rotated ears 33 HP:0000368
15 downslanted palpebral fissures 33 HP:0000494
16 triangular face 33 HP:0000325
17 generalized hypotonia 33 HP:0001290
18 cafe-au-lait spot 33 HP:0000957
19 neurofibromas 33 HP:0001067
20 axillary freckling 33 HP:0000997

Symptoms via clinical synopsis from OMIM:

58
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

MGI Mouse Phenotypes related to Legius Syndrome:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.55 NF1 PTPN11 SPRED1 SPRY2 SPRY4
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
2 Prevalence of Constitutional Mismatch-repair Deficiency Among Suspected Neurofibromatosis Type 1/Legius Syndrome Children Without a Malignancy and Without a NF1 or SPRED1 Mutation Not yet recruiting NCT03757247

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 30 SPRED1

Anatomical Context for Legius Syndrome

MalaCards organs/tissues related to Legius Syndrome:

42
Skin, Bone, Testes, Brain, Colon, Eye, Appendix

Publications for Legius Syndrome

Articles related to Legius Syndrome:

(show all 30)
# Title Authors Year
1
Correction: The absence that makes the difference: choroidal abnormalities in Legius syndrome. ( 29479078 )
2018
2
The first Slovak Legius syndrome patient carrying the SPRED1 gene mutation. ( 28150585 )
2017
3
Legius syndrome: A case report. ( 28378438 )
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
SPRED1, a RAS MAPK pathway inhibitor that causes Legius syndrome, is a tumour suppressor downregulated in paediatric acute myeloblastic leukaemia. ( 24469042 )
2015
7
Legius syndrome: case report and review of literature. ( 25883013 )
2015
8
Family with Legius syndrome (neurofibromatosis type 1-like syndrome). ( 25981987 )
2015
9
Legius Syndrome: two novel mutations in the SPRED1 gene. ( 27081556 )
2015
10
Legius syndrome, an Update. Molecular pathology of mutations in SPRED1. ( 24334617 )
2013
11
Café-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome. ( 22438235 )
2012
12
A shared molecular mechanism underlies the human rasopathies Legius syndrome and Neurofibromatosis-1. ( 22751498 )
2012
13
Review and update of SPRED1 mutations causing Legius syndrome. ( 22753041 )
2012
14
Legius syndrome in fourteen families. ( 21089071 )
2011
15
Observations on intelligence and behavior in 15 patients with Legius syndrome. ( 21495177 )
2011
16
Identification of five novel SPRED1 germline mutations in Legius syndrome. ( 21649642 )
2011
17
The SPRED1 Variants Repository for Legius Syndrome. ( 22384355 )
2011
18
Novel human pathological mutations. Gene symbol: SPRED1. Disease: Legius syndrome. ( 20108385 )
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. ( 20108420 )
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
Error in a study of the clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. ( 20571013 )
2010
24
Expanding the phenotype of a neurofibromatosis type 1-like syndrome: a patient with SPRED1 mutation and orbital manifestations: retraction. ( 20305530 )
2010
25
SPRED1 mutations (Legius syndrome): another clinically useful genotype for dissecting the neurofibromatosis type 1 phenotype. ( 19443465 )
2009
26
Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. ( 19920242 )
2009
27
Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. ( 19920235 )
2009
28
Expanding the phenotype of a neurofibromatosis type 1-like syndrome: a patient with a SPRED1 mutation and orbital manifestations. ( 19966658 )
2009
29
SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. ( 19366998 )
2009
30
Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. ( 17704776 )
2007

Variations for Legius Syndrome

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

76
# 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 352)
# Gene Variation Type Significance SNP ID Assembly Location
1 SPRED1 NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter) single nucleotide variant Pathogenic rs121434312 GRCh38 Chromosome 15, 38322382: 38322382
2 SPRED1 NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic rs121434313 GRCh37 Chromosome 15, 38591611: 38591611
3 SPRED1 NM_152594.2(SPRED1): c.70C> T (p.Arg24Ter) single nucleotide variant Pathogenic rs121434313 GRCh38 Chromosome 15, 38299410: 38299410
4 SPRED1 NM_152594.3(SPRED1): c.423+1G> A single nucleotide variant Pathogenic GRCh38 Chromosome 15, 38324810: 38324810
5 SPRED1 NM_152594.3(SPRED1): c.423+1G> A single nucleotide variant Pathogenic GRCh37 Chromosome 15, 38617011: 38617011
6 SPRED1 NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter) single nucleotide variant Pathogenic rs121434314 GRCh37 Chromosome 15, 38641683: 38641683
7 SPRED1 NM_152594.2(SPRED1): c.643C> T (p.Gln215Ter) single nucleotide variant Pathogenic rs121434314 GRCh38 Chromosome 15, 38349482: 38349482
8 SPRED1 NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter) single nucleotide variant Pathogenic rs121434315 GRCh37 Chromosome 15, 38591731: 38591731
9 SPRED1 NM_152594.2(SPRED1): c.349C> T (p.Arg117Ter) single nucleotide variant Pathogenic rs121434312 GRCh37 Chromosome 15, 38614583: 38614583
10 SPRED1 NM_152594.2(SPRED1): c.190C> T (p.Arg64Ter) single nucleotide variant Pathogenic rs121434315 GRCh38 Chromosome 15, 38299530: 38299530
11 SPRED1 NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter) single nucleotide variant Pathogenic rs121434316 GRCh37 Chromosome 15, 38641677: 38641677
12 SPRED1 NM_152594.2(SPRED1): c.637C> T (p.Gln213Ter) single nucleotide variant Pathogenic rs121434316 GRCh38 Chromosome 15, 38349476: 38349476
13 SPRED1 NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter) single nucleotide variant Pathogenic rs121434317 GRCh37 Chromosome 15, 38643314: 38643314
14 SPRED1 NM_152594.2(SPRED1): c.784A> T (p.Arg262Ter) single nucleotide variant Pathogenic rs121434317 GRCh38 Chromosome 15, 38351113: 38351113
15 SPRED1 NM_152594.2(SPRED1): c.131T> A (p.Val44Asp) single nucleotide variant Pathogenic rs121434318 GRCh37 Chromosome 15, 38591672: 38591672
16 SPRED1 NM_152594.2(SPRED1): c.131T> A (p.Val44Asp) single nucleotide variant Pathogenic rs121434318 GRCh38 Chromosome 15, 38299471: 38299471
17 BMPR2 NM_001204.6(BMPR2): c.545G> A (p.Gly182Asp) single nucleotide variant Uncertain significance rs137852754 GRCh37 Chromosome 2, 203379626: 203379626
18 BMPR2 NM_001204.6(BMPR2): c.545G> A (p.Gly182Asp) single nucleotide variant Uncertain significance rs137852754 GRCh38 Chromosome 2, 202514903: 202514903
19 SPRED1 NM_152594.3(SPRED1): c.1045_1046del (p.Arg349Glyfs) deletion Pathogenic GRCh38 Chromosome 15, 38351374: 38351375
20 SPRED1 NM_152594.3(SPRED1): c.1045_1046del (p.Arg349Glyfs) deletion Pathogenic GRCh37 Chromosome 15, 38643575: 38643576
21 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh37 Chromosome 12, 112926873: 112926873
22 PTPN11 NM_002834.4(PTPN11): c.1493G> T (p.Arg498Leu) single nucleotide variant Pathogenic rs397507542 GRCh38 Chromosome 12, 112489069: 112489069
23 SPRED1 NM_152594.2(SPRED1): c.1044T> C (p.Val348=) single nucleotide variant Benign/Likely benign rs3751526 GRCh37 Chromosome 15, 38643574: 38643574
24 SPRED1 NM_152594.2(SPRED1): c.1044T> C (p.Val348=) single nucleotide variant Benign/Likely benign rs3751526 GRCh38 Chromosome 15, 38351373: 38351373
25 SPRED1 NM_152594.2(SPRED1): c.291G> A (p.Lys97=) single nucleotide variant Benign/Likely benign rs7182445 GRCh37 Chromosome 15, 38614525: 38614525
26 SPRED1 NM_152594.2(SPRED1): c.291G> A (p.Lys97=) single nucleotide variant Benign/Likely benign rs7182445 GRCh38 Chromosome 15, 38322324: 38322324
27 SPRED1 NM_152594.2(SPRED1): c.424-8C= single nucleotide variant Benign rs7180446 GRCh37 Chromosome 15, 38631930: 38631930
28 SPRED1 NM_152594.2(SPRED1): c.424-8C= single nucleotide variant Benign rs7180446 GRCh38 Chromosome 15, 38339729: 38339729
29 SPRED1 NM_152594.2(SPRED1): c.424-98T= single nucleotide variant Benign rs7163339 GRCh37 Chromosome 15, 38631840: 38631840
30 SPRED1 NM_152594.2(SPRED1): c.424-98T= single nucleotide variant Benign rs7163339 GRCh38 Chromosome 15, 38339639: 38339639
31 SPRED1 NM_152594.2(SPRED1): c.424-18G> A single nucleotide variant Benign rs7179118 GRCh37 Chromosome 15, 38631920: 38631920
32 SPRED1 NM_152594.2(SPRED1): c.424-18G> A single nucleotide variant Benign rs7179118 GRCh38 Chromosome 15, 38339719: 38339719
33 SPRED1 NM_152594.2(SPRED1): c.424-8C> A single nucleotide variant Benign/Likely benign rs7180446 GRCh37 Chromosome 15, 38631930: 38631930
34 SPRED1 NM_152594.2(SPRED1): c.424-8C> A single nucleotide variant Benign/Likely benign rs7180446 GRCh38 Chromosome 15, 38339729: 38339729
35 SPRED1 NM_152594.2(SPRED1): c.124G> A (p.Val42Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs147204964 GRCh37 Chromosome 15, 38591665: 38591665
36 SPRED1 NM_152594.2(SPRED1): c.124G> A (p.Val42Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs147204964 GRCh38 Chromosome 15, 38299464: 38299464
37 SPRED1 NM_152594.2(SPRED1): c.177T> C (p.Phe59=) single nucleotide variant Likely benign rs397517871 GRCh37 Chromosome 15, 38591718: 38591718
38 SPRED1 NM_152594.2(SPRED1): c.177T> C (p.Phe59=) single nucleotide variant Likely benign rs397517871 GRCh38 Chromosome 15, 38299517: 38299517
39 SPRED1 NM_152594.2(SPRED1): c.26A> T (p.Asp9Val) single nucleotide variant Conflicting interpretations of pathogenicity rs200157475 GRCh37 Chromosome 15, 38545412: 38545412
40 SPRED1 NM_152594.2(SPRED1): c.26A> T (p.Asp9Val) single nucleotide variant Conflicting interpretations of pathogenicity rs200157475 GRCh38 Chromosome 15, 38253211: 38253211
41 SPRED1 NM_152594.2(SPRED1): c.377-10A> G single nucleotide variant Likely benign rs376134678 GRCh37 Chromosome 15, 38616954: 38616954
42 SPRED1 NM_152594.2(SPRED1): c.377-10A> G single nucleotide variant Likely benign rs376134678 GRCh38 Chromosome 15, 38324753: 38324753
43 SPRED1 NM_152594.2(SPRED1): c.583-7A> G single nucleotide variant Benign/Likely benign rs115970207 GRCh37 Chromosome 15, 38641616: 38641616
44 SPRED1 NM_152594.2(SPRED1): c.583-7A> G single nucleotide variant Benign/Likely benign rs115970207 GRCh38 Chromosome 15, 38349415: 38349415
45 SPRED1 NM_152594.2(SPRED1): c.675C> T (p.Ser225=) single nucleotide variant Benign rs144764225 GRCh37 Chromosome 15, 38641715: 38641715
46 SPRED1 NM_152594.2(SPRED1): c.675C> T (p.Ser225=) single nucleotide variant Benign rs144764225 GRCh38 Chromosome 15, 38349514: 38349514
47 SPRED1 NM_152594.2(SPRED1): c.702C> G (p.Ile234Met) single nucleotide variant Conflicting interpretations of pathogenicity rs138553244 GRCh37 Chromosome 15, 38643232: 38643232
48 SPRED1 NM_152594.2(SPRED1): c.702C> G (p.Ile234Met) single nucleotide variant Conflicting interpretations of pathogenicity rs138553244 GRCh38 Chromosome 15, 38351031: 38351031
49 SPRED1 NM_152594.2(SPRED1): c.926T> C (p.Val309Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs114636635 GRCh38 Chromosome 15, 38351255: 38351255
50 SPRED1 NM_152594.2(SPRED1): c.926T> C (p.Val309Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs114636635 GRCh37 Chromosome 15, 38643456: 38643456

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

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 29)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.95 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 metanephros development GO:0001656 9.64 NF1 SPRY1
5 mismatch repair GO:0006298 9.64 MSH2 MSH6
6 negative regulation of epidermal growth factor receptor signaling pathway GO:0042059 9.63 SPRY1 SPRY2
7 negative regulation of MAPK cascade GO:0043409 9.63 NF1 SPRED1
8 inactivation of MAPK activity GO:0000188 9.62 SPRED1 SPRED2
9 establishment of mitotic spindle orientation GO:0000132 9.62 SPRY1 SPRY2
10 negative regulation of ERK1 and ERK2 cascade GO:0070373 9.62 SPRED1 SPRY1 SPRY2 SPRY4
11 negative regulation of DNA recombination GO:0045910 9.61 MSH2 MSH6
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 positive regulation of helicase activity GO:0051096 9.56 MSH2 MSH6
17 negative regulation of fibroblast growth factor receptor signaling pathway GO:0040037 9.56 SPRY1 SPRY2 SPRY3 SPRY4
18 bud elongation involved in lung branching GO:0060449 9.55 SPRY1 SPRY2
19 negative regulation of MAP kinase activity GO:0043407 9.55 NF1 SPRY1 SPRY2 SPRY3 SPRY4
20 negative regulation of peptidyl-threonine phosphorylation GO:0010801 9.54 SPRED1 SPRED2 SPRY2
21 maintenance of DNA repeat elements GO:0043570 9.51 MSH2 MSH6
22 negative regulation of neurotrophin TRK receptor signaling pathway GO:0051387 9.48 SPRY1 SPRY2
23 somatic recombination of immunoglobulin gene segments GO:0016447 9.46 MSH2 MSH6
24 regulation of protein deacetylation GO:0090311 9.43 SPRED1 SPRED2
25 negative regulation of Ras protein signal transduction GO:0046580 9.35 NF1 SPRY1 SPRY2 SPRY3 SPRY4
26 pyrimidine dimer repair GO:0006290 9.24 MSH6
27 replication fork arrest GO:0043111 9.22 MSH6
28 meiotic mismatch repair GO:0000710 9.19 MSH6
29 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 12)
# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.72 MSH2 PTPN11 SPRED1 SPRED2 SPRY2
2 ADP binding GO:0043531 9.51 MSH2 MSH6
3 four-way junction DNA binding GO:0000400 9.49 MSH2 MSH6
4 mismatched DNA binding GO:0030983 9.48 MSH2 MSH6
5 MutLalpha complex binding GO:0032405 9.46 MSH2 MSH6
6 oxidized purine DNA binding GO:0032357 9.43 MSH2 MSH6
7 DNA-dependent ATPase activity GO:0008094 9.43 BPTF MSH2 MSH6
8 guanine/thymine mispair binding GO:0032137 9.4 MSH2 MSH6
9 single thymine insertion binding GO:0032143 9.37 MSH2 MSH6
10 single guanine insertion binding GO:0032142 9.16 MSH2 MSH6
11 stem cell factor receptor binding GO:0005173 8.96 SPRED1 SPRED2
12 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 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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