NS8
MCID: NNN021
MIFTS: 39

Noonan Syndrome 8 (NS8)

Categories: Cardiovascular diseases, Ear diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Noonan Syndrome 8

Summaries for Noonan Syndrome 8

UniProtKB/Swiss-Prot : 72 Noonan syndrome 8: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.

MalaCards based summary : Noonan Syndrome 8, also known as ns8, is related to otomycosis and external ear disease. An important gene associated with Noonan Syndrome 8 is RIT1 (Ras Like Without CAAX 1). Affiliated tissues include eye, bone marrow and t cells, and related phenotypes are intellectual disability and short stature

Disease Ontology : 12 A Noonan syndrome that has material basis in aused by heterozygous mutation in the RIT1 gene on chromosome 1q22.

OMIM® : 57 Noonan syndrome-8 is an autosomal dominant disorder characterized by short stature, distinctive facial features, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. A subset of patients show intellectual disabilities (summary by Aoki et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of Noonan syndrome, see NS1 (163950). (615355) (Updated 20-May-2021)

Related Diseases for Noonan Syndrome 8

Graphical network of the top 20 diseases related to Noonan Syndrome 8:



Diseases related to Noonan Syndrome 8

Symptoms & Phenotypes for Noonan Syndrome 8

Human phenotypes related to Noonan Syndrome 8:

31 (show all 26)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 31 very rare (1%) HP:0001249
2 short stature 31 very rare (1%) HP:0004322
3 cryptorchidism 31 very rare (1%) HP:0000028
4 webbed neck 31 very rare (1%) HP:0000465
5 left ventricular hypertrophy 31 very rare (1%) HP:0001712
6 patent ductus arteriosus 31 very rare (1%) HP:0001643
7 hyperextensible skin 31 very rare (1%) HP:0000974
8 relative macrocephaly 31 very rare (1%) HP:0004482
9 curly hair 31 very rare (1%) HP:0002212
10 hyperpigmentation of the skin 31 very rare (1%) HP:0000953
11 palmoplantar cutis laxa 31 very rare (1%) HP:0007517
12 abnormal sternum morphology 31 very rare (1%) HP:0000766
13 failure to thrive 31 HP:0001508
14 ptosis 31 HP:0000508
15 short neck 31 HP:0000470
16 hypertelorism 31 HP:0000316
17 hyperkeratosis 31 HP:0000962
18 low-set ears 31 HP:0000369
19 epicanthus 31 HP:0000286
20 atrial septal defect 31 HP:0001631
21 hypertrophic cardiomyopathy 31 HP:0001639
22 downslanted palpebral fissures 31 HP:0000494
23 polyhydramnios 31 HP:0001561
24 ventricular septal defect 31 HP:0001629
25 pulmonic stenosis 31 HP:0001642
26 pleural effusion 31 HP:0002202

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Growth Other:
failure to thrive

Head And Neck Neck:
short neck
webbed neck

Skin Nails Hair Skin:
hyperkeratosis
hyperelastic skin

Head And Neck Ears:
low-set ears

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
fetal pleural effusion

Skin Nails Hair Hair:
curly hair

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

Growth Height:
short stature

Genitourinary Internal Genitalia Male:
cryptorchidism

Cardiovascular Heart:
atrial septal defect
hypertrophic cardiomyopathy
ventricular septal defect
pulmonic stenosis
valvular insufficiency

Head And Neck Head:
relative macrocephaly

Neurologic Central Nervous System:
intellectual disability (in some patients)

Clinical features from OMIM®:

615355 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Noonan Syndrome 8 according to GeneCards Suite gene sharing:

26 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.44 RIT1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.44 GALE
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-123 9.44 RIT1
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-15 9.44 GALE
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-16 9.44 GALE
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-163 9.44 GALE
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-166 9.44 GALE
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.44 RIT1
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-214 9.44 RIT1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.44 RIT1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.44 GALE
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-74 9.44 GALE
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.44 GALE

Drugs & Therapeutics for Noonan Syndrome 8

Search Clinical Trials , NIH Clinical Center for Noonan Syndrome 8

Genetic Tests for Noonan Syndrome 8

Genetic tests related to Noonan Syndrome 8:

# Genetic test Affiliating Genes
1 Noonan Syndrome 8 29 RIT1

Anatomical Context for Noonan Syndrome 8

MalaCards organs/tissues related to Noonan Syndrome 8:

40
Eye, Bone Marrow, T Cells, Skin, Bone, Heart

Publications for Noonan Syndrome 8

Articles related to Noonan Syndrome 8:

(show all 22)
# Title Authors PMID Year
1
Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation. 57 6
27101134 2016
2
Mutations in RIT1 cause Noonan syndrome with possible juvenile myelomonocytic leukemia but are not involved in acute lymphoblastic leukemia. 57 6
26757980 2016
3
Spectrum of mutations and genotype-phenotype analysis in Noonan syndrome patients with RIT1 mutations. 57 6
26714497 2016
4
Further evidence of the importance of RIT1 in Noonan syndrome. 57 6
25124994 2014
5
Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity. 57 6
24939608 2014
6
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. 6 57
23791108 2013
7
RIT1 controls actin dynamics via complex formation with RAC1/CDC42 and PAK1. 6
29734338 2018
8
Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies. 6
29402968 2018
9
Response to Calgani et al. 57
27684038 2016
10
Congenital heart defects in Noonan syndrome and RIT1 mutation. 57
27684039 2016
11
Two cases of RIT1 associated Noonan syndrome: Further delineation of the clinical phenotype and review of the literature. 6
27109146 2016
12
Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1). 6
27226556 2016
13
The lymphatic phenotype in Noonan and Cardiofaciocutaneous syndrome. 6
26242988 2016
14
Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype. 6
25959749 2016
15
Recent advances in RASopathies. 6
26446362 2016
16
The usefulness of whole-exome sequencing in routine clinical practice. 6
24901346 2014
17
Next-generation sequencing identifies rare variants associated with Noonan syndrome. 6
25049390 2014
18
Oncogenic RIT1 mutations in lung adenocarcinoma. 6
24469055 2014
19
[Bone marrow transplantation: principles, indications and results]. 6
2657980 1989
20
Lichenoid tissue reaction (LTR) induced by local transfer of Ia-reactive T-cell clones. II. LTR by epidermal invasion of cytotoxic lymphokine-producing autoreactive T cells. 6
2439608 1987
21
Medical ethics and torture. 6
7109146 1982
22
Orthopaedic conditions in Ras/MAPK related disorders. 61
21654472 2011

Variations for Noonan Syndrome 8

ClinVar genetic disease variations for Noonan Syndrome 8:

6 (show all 50)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 RIT1 NM_006912.6(RIT1):c.170C>G (p.Ala57Gly) SNV Pathogenic 60506 rs672601334 GRCh37: 1:155874589-155874589
GRCh38: 1:155904798-155904798
2 RIT1 NM_006912.6(RIT1):c.242A>G (p.Glu81Gly) SNV Pathogenic 183405 rs869025193 GRCh37: 1:155874289-155874289
GRCh38: 1:155904498-155904498
3 RIT1 NM_006912.6(RIT1):c.246T>G (p.Phe82Leu) SNV Pathogenic 181522 rs730881014 GRCh37: 1:155874285-155874285
GRCh38: 1:155904494-155904494
4 RIT1 NM_006912.6(RIT1):c.244T>G (p.Phe82Val) SNV Pathogenic 183408 rs869025194 GRCh37: 1:155874287-155874287
GRCh38: 1:155904496-155904496
5 RIT1 NM_006912.6(RIT1):c.246T>A (p.Phe82Leu) SNV Pathogenic 370035 rs730881014 GRCh37: 1:155874285-155874285
GRCh38: 1:155904494-155904494
6 RIT1 NM_006912.6(RIT1):c.229G>C (p.Ala77Pro) SNV Pathogenic 228289 rs869025191 GRCh37: 1:155874530-155874530
GRCh38: 1:155904739-155904739
7 RIT1 NM_006912.6(RIT1):c.69A>C (p.Lys23Asn) SNV Pathogenic 581105 rs1557962794 GRCh37: 1:155880484-155880484
GRCh38: 1:155910693-155910693
8 RIT1 NM_006912.6(RIT1):c.265T>C (p.Tyr89His) SNV Pathogenic 183411 rs869025197 GRCh37: 1:155874266-155874266
GRCh38: 1:155904475-155904475
9 RIT1 NM_006912.6(RIT1):c.270G>T (p.Met90Ile) SNV Pathogenic 265328 rs483352822 GRCh37: 1:155874261-155874261
GRCh38: 1:155904470-155904470
10 RIT1 NM_006912.6(RIT1):c.268A>G (p.Met90Val) SNV Pathogenic 561681 rs1557960039 GRCh37: 1:155874263-155874263
GRCh38: 1:155904472-155904472
11 RIT1 NM_006912.6(RIT1):c.104G>C (p.Ser35Thr) SNV Pathogenic 183401 rs869025189 GRCh37: 1:155880449-155880449
GRCh38: 1:155910658-155910658
12 RIT1 NM_006912.6(RIT1):c.365G>T (p.Arg122Leu) SNV Pathogenic 280609 rs777520196 GRCh37: 1:155874166-155874166
GRCh38: 1:155904375-155904375
13 RIT1 NM_006912.6(RIT1):c.230C>G (p.Ala77Gly) SNV Pathogenic 850519 GRCh37: 1:155874529-155874529
GRCh38: 1:155904738-155904738
14 RIT1 NM_006912.6(RIT1):c.284G>C (p.Gly95Ala) SNV Pathogenic 60509 rs672601335 GRCh37: 1:155874247-155874247
GRCh38: 1:155904456-155904456
15 RIT1 NM_006912.6(RIT1):c.270G>C (p.Met90Ile) SNV Pathogenic 190305 rs483352822 GRCh37: 1:155874261-155874261
GRCh38: 1:155904470-155904470
16 RIT1 NM_006912.6(RIT1):c.229G>A (p.Ala77Thr) SNV Pathogenic/Likely pathogenic 183403 rs869025191 GRCh37: 1:155874530-155874530
GRCh38: 1:155904739-155904739
17 RIT1 NM_006912.6(RIT1):c.233G>A (p.Gly78Glu) SNV Likely pathogenic 560679 rs1557960268 GRCh37: 1:155874526-155874526
GRCh38: 1:155904735-155904735
18 RIT1 NM_006912.6(RIT1):c.268A>C (p.Met90Leu) SNV Likely pathogenic 976308 GRCh37: 1:155874263-155874263
GRCh38: 1:155904472-155904472
19 RIT1 NM_006912.6(RIT1):c.67A>C (p.Lys23Gln) SNV Conflicting interpretations of pathogenicity 224122 rs869312687 GRCh37: 1:155880486-155880486
GRCh38: 1:155910695-155910695
20 RIT1 NM_006912.6(RIT1):c.244T>A (p.Phe82Ile) SNV Uncertain significance 183406 rs869025194 GRCh37: 1:155874287-155874287
GRCh38: 1:155904496-155904496
21 RIT1 NM_006912.6(RIT1):c.334C>T (p.Arg112Cys) SNV Uncertain significance 404258 rs375724784 GRCh37: 1:155874197-155874197
GRCh38: 1:155904406-155904406
22 RIT1 NM_006912.6(RIT1):c.153T>G (p.Asp51Glu) SNV Uncertain significance 648447 rs1571999275 GRCh37: 1:155880251-155880251
GRCh38: 1:155910460-155910460
23 RIT1 NM_006912.6(RIT1):c.461G>A (p.Arg154Gln) SNV Uncertain significance 653052 rs754596127 GRCh37: 1:155870378-155870378
GRCh38: 1:155900587-155900587
24 RIT1 NM_006912.6(RIT1):c.13A>T (p.Thr5Ser) SNV Uncertain significance 662410 rs771768320 GRCh37: 1:155880540-155880540
GRCh38: 1:155910749-155910749
25 RIT1 NM_006912.6(RIT1):c.575C>T (p.Ala192Val) SNV Uncertain significance 280768 rs376391961 GRCh37: 1:155870264-155870264
GRCh38: 1:155900473-155900473
26 RIT1 NM_006912.6(RIT1):c.546A>G (p.Ile182Met) SNV Uncertain significance 1003981 GRCh37: 1:155870293-155870293
GRCh38: 1:155900502-155900502
27 RIT1 NM_006912.6(RIT1):c.257G>A (p.Arg86Gln) SNV Uncertain significance 1006457 GRCh37: 1:155874274-155874274
GRCh38: 1:155904483-155904483
28 RIT1 NM_006912.6(RIT1):c.229_234dup (p.Ala77_Gly78dup) Duplication Uncertain significance 1007287 GRCh37: 1:155874524-155874525
GRCh38: 1:155904733-155904734
29 RIT1 NM_006912.6(RIT1):c.368G>A (p.Arg123His) SNV Uncertain significance 1009476 GRCh37: 1:155874163-155874163
GRCh38: 1:155904372-155904372
30 RIT1 NC_000001.10:g.(?_155870159)_(155880696_?)dup Duplication Uncertain significance 1015626 GRCh37: 1:155870159-155880696
GRCh38:
31 RIT1 NM_006912.6(RIT1):c.134G>T (p.Arg45Leu) SNV Uncertain significance 1022388 GRCh37: 1:155880270-155880270
GRCh38: 1:155910479-155910479
32 RIT1 NM_006912.6(RIT1):c.506A>G (p.Tyr169Cys) SNV Uncertain significance 917582 GRCh37: 1:155870333-155870333
GRCh38: 1:155900542-155900542
33 RIT1 NM_006912.6(RIT1):c.634C>T (p.Arg212Trp) SNV Uncertain significance 280150 rs563231684 GRCh37: 1:155870205-155870205
GRCh38: 1:155900414-155900414
34 RIT1 NC_000001.10:g.(?_155874092)_(155880686_?)dup Duplication Uncertain significance 1040782 GRCh37: 1:155874092-155880686
GRCh38:
35 RIT1 NM_006912.6(RIT1):c.113C>G (p.Thr38Ser) SNV Uncertain significance 1053927 GRCh37: 1:155880291-155880291
GRCh38: 1:155910500-155910500
36 RIT1 NM_006912.6(RIT1):c.116T>A (p.Met39Lys) SNV Uncertain significance 1063825 GRCh37: 1:155880288-155880288
GRCh38: 1:155910497-155910497
37 overlap with 10 genes NC_000001.10:g.(?_155880221)_(156109650_?)del Deletion Uncertain significance 477767 GRCh37: 1:155880221-156109650
GRCh38:
38 RIT1 NM_006912.6(RIT1):c.112A>G (p.Thr38Ala) SNV Uncertain significance 577778 rs1557962699 GRCh37: 1:155880292-155880292
GRCh38: 1:155910501-155910501
39 RIT1 NM_006912.6(RIT1):c.640_643AAGA[1] (p.Lys215fs) Microsatellite Uncertain significance 506383 rs766063111 GRCh37: 1:155870192-155870195
GRCh38: 1:155900401-155900404
40 RIT1 NM_006912.6(RIT1):c.163+5G>T SNV Uncertain significance 838350 GRCh37: 1:155880236-155880236
GRCh38: 1:155910445-155910445
41 RIT1 NM_006912.6(RIT1):c.649del (p.Ser217fs) Deletion Uncertain significance 839801 GRCh37: 1:155870190-155870190
GRCh38: 1:155900399-155900399
42 RIT1 NM_006912.6(RIT1):c.140C>T (p.Pro47Leu) SNV Uncertain significance 842237 GRCh37: 1:155880264-155880264
GRCh38: 1:155910473-155910473
43 RIT1 NM_006912.6(RIT1):c.367C>T (p.Arg123Cys) SNV Uncertain significance 936786 GRCh37: 1:155874164-155874164
GRCh38: 1:155904373-155904373
44 RIT1 NM_006912.6(RIT1):c.151G>T (p.Asp51Tyr) SNV Uncertain significance 183402 rs869025190 GRCh37: 1:155880253-155880253
GRCh38: 1:155910462-155910462
45 RIT1 NM_006912.6(RIT1):c.237+10C>A SNV Likely benign 477768 rs367785615 GRCh37: 1:155874512-155874512
GRCh38: 1:155904721-155904721
46 RIT1 NM_006912.6(RIT1):c.393T>C (p.Leu131=) SNV Likely benign 516224 rs34974790 GRCh37: 1:155874138-155874138
GRCh38: 1:155904347-155904347
47 RIT1 NM_006912.6(RIT1):c.107-9C>G SNV Likely benign 701093 rs200597833 GRCh37: 1:155880306-155880306
GRCh38: 1:155910515-155910515
48 RIT1 NM_006912.6(RIT1):c.540G>A (p.Arg180=) SNV Likely benign 757796 rs369738767 GRCh37: 1:155870299-155870299
GRCh38: 1:155900508-155900508
49 RIT1 NM_006912.6(RIT1):c.375C>T (p.Asp125=) SNV Benign 197790 rs34831194 GRCh37: 1:155874156-155874156
GRCh38: 1:155904365-155904365
50 RIT1 NM_006912.6(RIT1):c.270G>A (p.Met90Ile) SNV not provided 120250 rs483352822 GRCh37: 1:155874261-155874261
GRCh38: 1:155904470-155904470

UniProtKB/Swiss-Prot genetic disease variations for Noonan Syndrome 8:

72
# Symbol AA change Variation ID SNP ID
1 RIT1 p.Ala57Gly VAR_070150 rs672601334
2 RIT1 p.Glu81Gly VAR_070151 rs869025193
3 RIT1 p.Phe82Leu VAR_070152 rs730881014
4 RIT1 p.Met90Ile VAR_070156 rs483352822
5 RIT1 p.Gly95Ala VAR_070157 rs672601335

Expression for Noonan Syndrome 8

Search GEO for disease gene expression data for Noonan Syndrome 8.

Pathways for Noonan Syndrome 8

GO Terms for Noonan Syndrome 8

Biological processes related to Noonan Syndrome 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 galactose metabolic process GO:0006012 8.96 GALK1 GALE
2 galactose catabolic process GO:0019388 8.62 GALK1 GALE

Sources for Noonan Syndrome 8

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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