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 : 76 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 dermatitis, atopic and dermatitis. An important gene associated with Noonan Syndrome 8 is RIT1 (Ras Like Without CAAX 1), and among its related pathways/superpathways are Galactose metabolism and Amino sugar and nucleotide sugar metabolism. The drugs Zidovudine and Miglustat have been mentioned in the context of this disorder. Affiliated tissues include skin and eye, 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 : 58 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)

Related Diseases for Noonan Syndrome 8

Diseases in the Noonan Syndrome 1 family:

Noonan Syndrome 2 Noonan Syndrome 3
Noonan Syndrome 4 Noonan Syndrome 5
Noonan Syndrome 6 Noonan Syndrome 7
Noonan Syndrome 8 Noonan Syndrome 9
Noonan Syndrome 10

Diseases related to Noonan Syndrome 8 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 dermatitis, atopic 10.1
2 dermatitis 10.1
3 epimerase deficiency galactosemia 9.8 GALE GALK1
4 galactosemia 9.8 GALE GALK1
5 galactose epimerase deficiency 9.7 GALE GALK1
6 galactokinase deficiency 9.6 GALE GALK1

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:

33 (show all 26)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 33 very rare (1%) HP:0001249
2 short stature 33 very rare (1%) HP:0004322
3 patent ductus arteriosus 33 very rare (1%) HP:0001643
4 cryptorchidism 33 very rare (1%) HP:0000028
5 webbed neck 33 very rare (1%) HP:0000465
6 left ventricular hypertrophy 33 very rare (1%) HP:0001712
7 curly hair 33 very rare (1%) HP:0002212
8 hyperextensible skin 33 very rare (1%) HP:0000974
9 abnormality of the sternum 33 very rare (1%) HP:0000766
10 relative macrocephaly 33 very rare (1%) HP:0004482
11 hyperpigmentation of the skin 33 very rare (1%) HP:0000953
12 palmoplantar cutis laxa 33 very rare (1%) HP:0007517
13 hypertelorism 33 HP:0000316
14 low-set ears 33 HP:0000369
15 short neck 33 HP:0000470
16 ptosis 33 HP:0000508
17 failure to thrive 33 HP:0001508
18 hypertrophic cardiomyopathy 33 HP:0001639
19 hyperkeratosis 33 HP:0000962
20 epicanthus 33 HP:0000286
21 atrial septal defect 33 HP:0001631
22 downslanted palpebral fissures 33 HP:0000494
23 polyhydramnios 33 HP:0001561
24 ventricular septal defect 33 HP:0001629
25 pulmonic stenosis 33 HP:0001642
26 pleural effusion 33 HP:0002202

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
ptosis
downslanting palpebral fissures
epicanthal folds

Head And Neck Neck:
short neck
webbed neck

Growth Height:
short stature

Skin Nails Hair Skin:
hyperkeratosis
hyperelastic skin

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
fetal pleural effusion

Head And Neck Head:
relative macrocephaly

Head And Neck Ears:
low-set ears

Growth Other:
failure to thrive

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

Genitourinary Internal Genitalia Male:
cryptorchidism

Skin Nails Hair Hair:
curly hair

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

Clinical features from OMIM:

615355

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

27 (show all 13)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-10 9.47 GALE RIT1
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.47 RIT1
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.47 GALE
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-117 9.47 RIT1
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-15 9.47 GALE
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-18 9.47 RIT1
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-212 9.47 GALE
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 9.47 GALE
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-38 9.47 RIT1
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-40 9.47 RIT1
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-48 9.47 RIT1
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-72 9.47 GALE
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-75 9.47 GALE

Drugs & Therapeutics for Noonan Syndrome 8

Drugs for Noonan Syndrome 8 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Zidovudine Approved Phase 2 30516-87-1 35370
2
Miglustat Approved Phase 2 72599-27-0 51634
3
1-Deoxynojirimycin Investigational Phase 2 19130-96-2 1374
4 Anti-Retroviral Agents Phase 2
5 Anti-Infective Agents Phase 2
6 Anti-HIV Agents Phase 2
7 Reverse Transcriptase Inhibitors Phase 2
8 Nucleic Acid Synthesis Inhibitors Phase 2
9 Antiviral Agents Phase 2
10 Antimetabolites Phase 2
11 Glycoside Hydrolase Inhibitors Phase 2
12 Hypoglycemic Agents Phase 2
13 Cardiac Glycosides Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase II Study of the Safety and Surrogate Marker Efficacy of Butyldeoxynojirimycin (SC-48334) and AZT in Symptomatic HIV-1 Infected Patients With 200 - 500 CD4+ Cells/mm3. (NOTE: Asymptomatic HIV-1 Infected Patients Also Eligible) Completed NCT00002079 Phase 2 Butyldeoxynojirimycin;Zidovudine
2 Initial Phase II Efficacy and Safety Study of SC-48334 Administered in Combination With Low-Dose Zidovudine (AZT) to Symptomatic HIV-1 Infected Patients With = or > 200 to = or < 500 CD4+ Cells/mm3 Completed NCT00001993 Phase 2 Butyldeoxynojirimycin;Zidovudine

Search 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 30 RIT1

Anatomical Context for Noonan Syndrome 8

MalaCards organs/tissues related to Noonan Syndrome 8:

42
Skin, Eye

Publications for Noonan Syndrome 8

Articles related to Noonan Syndrome 8:

# Title Authors Year
1
Oral Intake of Lactobacillus helveticus NS8 Alleviates Ovalbumin-Induced Atopic Dermatitis in SKH-1 Hairless Mice. ( 30013275 )
2018
2
Skin resistance to UVB-induced oxidative stress and hyperpigmentation by the topical use of Lactobacillus helveticus NS8-fermented milk supernatant. ( 28598022 )
2017
3
Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress. ( 26408987 )
2015
4
Probiotic and anti-inflammatory attributes of an isolate Lactobacillus helveticus NS8 from Mongolian fermented koumiss. ( 26428623 )
2015
5
Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: four new cases and further evidence of heterogeneity. ( 24939608 )
2014
6
Further evidence of the importance of RIT1 in Noonan syndrome. ( 25124994 )
2014
7
Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome. ( 23791108 )
2013

Variations for Noonan Syndrome 8

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

76
# 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

ClinVar genetic disease variations for Noonan Syndrome 8:

6 (show all 47)
# Gene Variation Type Significance SNP ID Assembly Location
1 RIT1 NM_006912.5(RIT1): c.170C> G (p.Ala57Gly) single nucleotide variant Pathogenic rs672601334 GRCh37 Chromosome 1, 155874589: 155874589
2 RIT1 NM_006912.5(RIT1): c.170C> G (p.Ala57Gly) single nucleotide variant Pathogenic rs672601334 GRCh38 Chromosome 1, 155904798: 155904798
3 RIT1 NM_006912.5(RIT1): c.284G> C (p.Gly95Ala) single nucleotide variant Pathogenic rs672601335 GRCh37 Chromosome 1, 155874247: 155874247
4 RIT1 NM_006912.5(RIT1): c.284G> C (p.Gly95Ala) single nucleotide variant Pathogenic rs672601335 GRCh38 Chromosome 1, 155904456: 155904456
5 RIT1 NM_006912.5(RIT1): c.270G> A (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh38 Chromosome 1, 155904470: 155904470
6 RIT1 NM_006912.5(RIT1): c.270G> A (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh37 Chromosome 1, 155874261: 155874261
7 RIT1 NM_006912.5(RIT1): c.246T> G (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh38 Chromosome 1, 155904494: 155904494
8 RIT1 NM_006912.5(RIT1): c.246T> G (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh37 Chromosome 1, 155874285: 155874285
9 RIT1 NM_006912.5(RIT1): c.265T> C (p.Tyr89His) single nucleotide variant Pathogenic rs869025197 GRCh38 Chromosome 1, 155904475: 155904475
10 RIT1 NM_006912.5(RIT1): c.265T> C (p.Tyr89His) single nucleotide variant Pathogenic rs869025197 GRCh37 Chromosome 1, 155874266: 155874266
11 RIT1 NM_006912.5(RIT1): c.244T> G (p.Phe82Val) single nucleotide variant Pathogenic rs869025194 GRCh38 Chromosome 1, 155904496: 155904496
12 RIT1 NM_006912.5(RIT1): c.244T> G (p.Phe82Val) single nucleotide variant Pathogenic rs869025194 GRCh37 Chromosome 1, 155874287: 155874287
13 RIT1 NM_006912.5(RIT1): c.244T> A (p.Phe82Ile) single nucleotide variant Uncertain significance rs869025194 GRCh38 Chromosome 1, 155904496: 155904496
14 RIT1 NM_006912.5(RIT1): c.244T> A (p.Phe82Ile) single nucleotide variant Uncertain significance rs869025194 GRCh37 Chromosome 1, 155874287: 155874287
15 RIT1 NM_006912.5(RIT1): c.242A> G (p.Glu81Gly) single nucleotide variant Pathogenic rs869025193 GRCh38 Chromosome 1, 155904498: 155904498
16 RIT1 NM_006912.5(RIT1): c.242A> G (p.Glu81Gly) single nucleotide variant Pathogenic rs869025193 GRCh37 Chromosome 1, 155874289: 155874289
17 RIT1 NM_006912.5(RIT1): c.229G> A (p.Ala77Thr) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh38 Chromosome 1, 155904739: 155904739
18 RIT1 NM_006912.5(RIT1): c.229G> A (p.Ala77Thr) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh37 Chromosome 1, 155874530: 155874530
19 RIT1 NM_006912.5(RIT1): c.104G> C (p.Ser35Thr) single nucleotide variant Pathogenic rs869025189 GRCh38 Chromosome 1, 155910658: 155910658
20 RIT1 NM_006912.5(RIT1): c.104G> C (p.Ser35Thr) single nucleotide variant Pathogenic rs869025189 GRCh37 Chromosome 1, 155880449: 155880449
21 RIT1 NM_006912.5(RIT1): c.270G> C (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh37 Chromosome 1, 155874261: 155874261
22 RIT1 NM_006912.5(RIT1): c.270G> C (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh38 Chromosome 1, 155904470: 155904470
23 RIT1 NM_001256821.1(RIT1): c.426C> T (p.Asp142=) single nucleotide variant Benign rs34831194 GRCh37 Chromosome 1, 155874156: 155874156
24 RIT1 NM_001256821.1(RIT1): c.426C> T (p.Asp142=) single nucleotide variant Benign rs34831194 GRCh38 Chromosome 1, 155904365: 155904365
25 RIT1 NM_006912.5(RIT1): c.67A> C (p.Lys23Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs869312687 GRCh37 Chromosome 1, 155880486: 155880486
26 RIT1 NM_006912.5(RIT1): c.67A> C (p.Lys23Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs869312687 GRCh38 Chromosome 1, 155910695: 155910695
27 RIT1 NM_006912.5(RIT1): c.229G> C (p.Ala77Pro) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh38 Chromosome 1, 155904739: 155904739
28 RIT1 NM_006912.5(RIT1): c.229G> C (p.Ala77Pro) single nucleotide variant Pathogenic/Likely pathogenic rs869025191 GRCh37 Chromosome 1, 155874530: 155874530
29 RIT1 NM_006912.5(RIT1): c.270G> T (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh37 Chromosome 1, 155874261: 155874261
30 RIT1 NM_006912.5(RIT1): c.270G> T (p.Met90Ile) single nucleotide variant Pathogenic rs483352822 GRCh38 Chromosome 1, 155904470: 155904470
31 RIT1 NM_006912.5(RIT1): c.246T> A (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh38 Chromosome 1, 155904494: 155904494
32 RIT1 NM_006912.5(RIT1): c.246T> A (p.Phe82Leu) single nucleotide variant Pathogenic rs730881014 GRCh37 Chromosome 1, 155874285: 155874285
33 RIT1 NM_006912.5(RIT1): c.334C> T (p.Arg112Cys) single nucleotide variant Uncertain significance rs375724784 GRCh37 Chromosome 1, 155874197: 155874197
34 RIT1 NM_006912.5(RIT1): c.334C> T (p.Arg112Cys) single nucleotide variant Uncertain significance rs375724784 GRCh38 Chromosome 1, 155904406: 155904406
35 RIT1 NC_000001.10: g.(?_155880221)_(156109650_?)del deletion Uncertain significance GRCh37 Chromosome 1, 155880221: 156109650
36 RIT1 NM_006912.5(RIT1): c.237+10C> A single nucleotide variant Benign/Likely benign rs367785615 GRCh37 Chromosome 1, 155874512: 155874512
37 RIT1 NM_006912.5(RIT1): c.237+10C> A single nucleotide variant Benign/Likely benign rs367785615 GRCh38 Chromosome 1, 155904721: 155904721
38 RIT1 NM_006912.5(RIT1): c.644_647delAAGA (p.Lys215Ilefs) deletion Conflicting interpretations of pathogenicity rs766063111 GRCh37 Chromosome 1, 155870192: 155870195
39 RIT1 NM_006912.5(RIT1): c.644_647delAAGA (p.Lys215Ilefs) deletion Conflicting interpretations of pathogenicity rs766063111 GRCh38 Chromosome 1, 155900401: 155900404
40 RIT1 NM_006912.5(RIT1): c.393T> C (p.Leu131=) single nucleotide variant Likely benign rs34974790 GRCh37 Chromosome 1, 155874138: 155874138
41 RIT1 NM_006912.5(RIT1): c.393T> C (p.Leu131=) single nucleotide variant Likely benign rs34974790 GRCh38 Chromosome 1, 155904347: 155904347
42 RIT1 NM_006912.5(RIT1): c.268A> G (p.Met90Val) single nucleotide variant Pathogenic GRCh37 Chromosome 1, 155874263: 155874263
43 RIT1 NM_006912.5(RIT1): c.268A> G (p.Met90Val) single nucleotide variant Pathogenic GRCh38 Chromosome 1, 155904472: 155904472
44 RIT1 NM_006912.5(RIT1): c.69A> C (p.Lys23Asn) single nucleotide variant Likely pathogenic GRCh37 Chromosome 1, 155880484: 155880484
45 RIT1 NM_006912.5(RIT1): c.69A> C (p.Lys23Asn) single nucleotide variant Likely pathogenic GRCh38 Chromosome 1, 155910693: 155910693
46 RIT1 NM_006912.5(RIT1): c.112A> G (p.Thr38Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 155880292: 155880292
47 RIT1 NM_006912.5(RIT1): c.112A> G (p.Thr38Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 155910501: 155910501

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 carbohydrate metabolic process GO:0005975 9.16 GALE GALK1
2 galactose metabolic process GO:0006012 8.96 GALE GALK1
3 galactose catabolic process GO:0019388 8.62 GALE GALK1

Sources for Noonan Syndrome 8

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
51 NCIt
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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