NETH
MCID: NTH001
MIFTS: 62

Netherton Syndrome (NETH)

Categories: Blood diseases, Ear diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases
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Aliases & Classifications for Netherton Syndrome

MalaCards integrated aliases for Netherton Syndrome:

Name: Netherton Syndrome 57 11 19 42 58 75 73 28 12 53 5 43 14 38
Comel-Netherton Syndrome 57 42 58 73
Netherton Disease 57 19 42 73
Neth 57 19 42 73
Ns 57 42 58 73
Erythroderma, Ichthyosiform, with Hypotrichosis and Hyper-Ige 57 73
Ichthyosis Linearis Circumflexa 42 71
Bamboo Hair Syndrome 42 58
Ichthyosiform Erythroderma with Hypotrichosis and Hyper-Ige 42
N Syndrome 71
Ilc 42
Nts 73

Characteristics:


Inheritance:

Autosomal recessive 58 57

Prevelance:

1-9/1000000 (Europe, Europe) 58

Age Of Onset:

Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
some severely affected infants die in the neonatal period


Classifications:

Orphanet: 58  
Rare skin diseases
Rare immunological diseases


Summaries for Netherton Syndrome

MedlinePlus Genetics: 42 Netherton syndrome is a disorder that affects the skin, hair, and immune system. Newborns with Netherton syndrome have skin that is red and scaly (ichthyosiform erythroderma), and the skin may leak fluid. Some affected infants are born with a tight, clear sheath covering their skin called a collodion membrane. This membrane is usually shed during the first few weeks of life. Because newborns with this disorder are missing the protection provided by normal skin, they are at risk of becoming dehydrated and developing infections in the skin or throughout the body (sepsis), which can be life-threatening. Affected babies may also fail to grow and gain weight at the expected rate (failure to thrive). The health of older children and adults with Netherton syndrome usually improves, although they often remain underweight and of short stature.After infancy, the severity of the skin abnormalities varies among people with Netherton syndrome and can fluctuate over time. The skin may continue to be red and scaly, especially during the first few years of life. Some affected individuals have intermittent redness or experience outbreaks of a distinctive skin abnormality called ichthyosis linearis circumflexa, involving patches of multiple ring-like lesions. The triggers for the outbreaks are not known, but researchers suggest that stress or infections may be involved.Itchiness is a common problem for affected individuals, and scratching can lead to frequent infections. Dead skin cells are shed at an abnormal rate and often accumulate in the ear canals, which can affect hearing if not removed regularly. The skin is abnormally absorbent of substances such as lotions and ointments, which can result in excessive blood levels of some topical medications. Because the ability of the skin to protect against heat and cold is impaired, affected individuals may have difficulty regulating their body temperature.People with Netherton syndrome have hair that is fragile and breaks easily. Some strands of hair vary in diameter, with thicker and thinner spots. This feature is known as bamboo hair, trichorrhexis nodosa, or trichorrhexis invaginata. In addition to the hair on the scalp, the eyelashes and eyebrows may be affected. The hair abnormality in Netherton syndrome may not be noticed in infancy because babies often have sparse hair.Most people with Netherton syndrome have immune system-related problems such as food allergies, hay fever, asthma, or an inflammatory skin disorder called eczema.

MalaCards based summary: Netherton Syndrome, also known as comel-netherton syndrome, is related to dermatitis, atopic and ichthyosis, and has symptoms including trichorrhexis invaginata An important gene associated with Netherton Syndrome is SPINK5 (Serine Peptidase Inhibitor Kazal Type 5), and among its related pathways/superpathways are Nervous system development and Collagen chain trimerization. The drugs HIV Protease Inhibitors and Serine Proteinase Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include skin, kidney and heart, and related phenotypes are malabsorption and asthma

OMIM®: 57 Netherton syndrome is a rare and severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Generalized scaly erythroderma is apparent at or soon after birth and usually persists. Scalp hair is sparse and brittle with a characteristic 'bamboo' shape under light microscopic examination due to invagination of the distal part of the hair shaft to its proximal part. Atopic manifestations include eczema-like rashes, atopic dermatitis, pruritus, hay fever, angioedema, urticaria, high levels of IgE in the serum, and hypereosinophilia. Life-threatening complications are frequent during the neonatal period, including hypernatremic dehydration, hypothermia, extreme weight loss, bronchopneumonia, and sepsis. During childhood, failure to thrive is common as a result of malnutrition, metabolic disorders, chronic erythroderma, persistent cutaneous infections, or enteropathy (summary by Bitoun et al., 2002). (256500) (Updated 08-Dec-2022)

GARD: 19 Netherton disease is a rare disorder affecting the skin, hair and immune system. Symptoms are present at birth and include red, scaly skin. Other symptoms include outbreaks of red, circular scaly rashes, thin, fragile hair (bamboo hair), and immune reactions such as hay fever, asthma, itchy skin, and eczema. Dehydration and infection are common and can be serious. Babies tend to grow slowly and have poor weight gain. Netherton syndrome is caused by the SPINK5 gene not working correctly. It is inherited in an autosomal recessive pattern. Netherton syndrome is diagnosed based on clinical examination, the symptoms, and genetic testing.

UniProtKB/Swiss-Prot: 73 An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.

Disease Ontology: 11 A skin disease that is characterized by chronic skin inflammation, trichorrhexis invaginata, atopic dermatitis and has material basis in mutations in the SPINK5 gene resulting in reduced capacity to inhibit serine proteases expressed in the skin.

Orphanet: 58 Netherton syndrome (NS) is a skin disorder characterized by congenital ichthyosiform erythroderma (CIE), a distinctive hair shaft defect (trichorrhexis invaginata; TI) and atopic manifestations.

Wikipedia: 75 Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the... more...

Related Diseases for Netherton Syndrome

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

(show top 50) (show all 265)
# Related Disease Score Top Affiliating Genes
1 dermatitis, atopic 31.0 TGM3 SPINK5 KLK7 KLK5 IGHE FLG
2 ichthyosis 30.9 TGM3 TGM1 SPINK5 KLK7 GBA1 FLG
3 dermatitis 30.6 SPINK5 KLK7 IGHE FLG DSG1
4 pustular psoriasis 30.6 PI3 ELANE
5 esophagitis, eosinophilic, 1 30.2 SPINK5 FLG DSG1
6 ritter's disease 30.2 DSG1 DSC1
7 ichthyosis vulgaris 29.8 TGM1 SPINK5 KLK7 KLK5 FLG DSG1
8 autosomal recessive congenital ichthyosis 29.6 TGM3 TGM1 SPINK5 KLK7 KLK6 KLK5
9 skin disease 29.5 TGM3 TGM1 SPINK5 PI3 KLK7 IGHE
10 peeling skin syndrome 29.3 TGM3 TGM1 SPINK5 KLK7 KLK6 FLG
11 psoriasis 29.3 TGM3 TGM1 SPINK5 PI3 KLK7 KLK6
12 prostate cancer 11.2
13 pancreatic cancer 11.2
14 hypertension, essential 11.1
15 sudden infant death syndrome 11.1
16 gastroesophageal reflux 11.1
17 schizophrenia 11.1
18 cystic fibrosis 11.1
19 short bowel syndrome 11.1
20 dumping syndrome 11.1
21 neuroendocrine tumor 11.1
22 duodenogastric reflux 11.1
23 vipoma 11.1
24 parkinson disease, late-onset 11.0
25 body mass index quantitative trait locus 11 11.0
26 diarrhea 11.0
27 lipofibromatosis-like neural tumor 11.0
28 alzheimer disease, familial, 1 11.0
29 type 2 diabetes mellitus 11.0
30 prader-willi syndrome 11.0
31 tobacco addiction 11.0
32 meningioma, familial 11.0
33 restless legs syndrome 11.0
34 zollinger-ellison syndrome 11.0
35 psychotic disorder 11.0
36 acute porphyria 11.0
37 eating disorder 11.0
38 pain agnosia 10.8
39 acute anterolateral myocardial infarction 10.8
40 functional gastric disease 10.8
41 alcoholic neuropathy 10.8
42 agnosia 10.8
43 fibrolamellar carcinoma 10.8
44 postgastrectomy syndrome 10.8
45 carcinoid syndrome 10.8
46 ige responsiveness, atopic 10.6
47 ichthyosis linearis circumflexa 10.6
48 erythrokeratoderma ''en cocardes'' 10.4
49 rare genetic skin disease 10.4
50 occupational dermatitis 10.3 KLK7 FLG

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



Diseases related to Netherton Syndrome

Symptoms & Phenotypes for Netherton Syndrome

Human phenotypes related to Netherton Syndrome:

58 30 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 malabsorption 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002024
2 asthma 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002099
3 sparse scalp hair 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002209
4 fine hair 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0002213
5 eczema 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000964
6 urticaria 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001025
7 acanthosis nigricans 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000956
8 irregular hyperpigmentation 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0007400
9 trichorrhexis nodosa 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0009886
10 congenital nonbullous ichthyosiform erythroderma 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0007479
11 increased circulating ige level 30 Hallmark (90%) HP:0003212
12 intellectual disability 58 30 Frequent (33%) Frequent (79-30%)
HP:0001249
13 seizure 58 30 Frequent (33%) Frequent (79-30%)
HP:0001250
14 global developmental delay 58 30 Frequent (33%) Frequent (79-30%)
HP:0001263
15 recurrent respiratory infections 58 30 Frequent (33%) Frequent (79-30%)
HP:0002205
16 emphysema 58 30 Frequent (33%) Frequent (79-30%)
HP:0002097
17 decreased circulating antibody level 30 Frequent (33%) HP:0004313
18 short stature 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0004322
19 dehydration 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001944
20 aminoaciduria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003355
21 dry skin 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000958
22 ectopic kidney 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000086
23 hydronephrosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000126
24 skin rash 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000988
25 erythroderma 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001019
26 sparse eyebrow 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0045075
27 sparse eyelashes 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000653
28 intestinal atresia 30 Very rare (1%) HP:0011100
29 recurrent infections 58 30 Occasional (29-5%)
HP:0002719
30 failure to thrive 30 HP:0001508
31 ichthyosis 58 Very frequent (99-80%)
32 decreased antibody level in blood 58 Frequent (79-30%)
33 abnormality of the hair 58 Very frequent (99-80%)
34 immunologic hypersensitivity 58 Very frequent (99-80%)
35 abnormality of the musculature 30 HP:0003011
36 angioedema 30 HP:0100665
37 increased circulating total ige level 58 Very frequent (99-80%)
38 brittle hair 30 HP:0002299
39 decreased circulating igg level 30 HP:0004315
40 hypereosinophilia 30 HP:0032061
41 parakeratosis 30 HP:0001036
42 villous atrophy 30 HP:0011473
43 allergic rhinitis 30 HP:0003193
44 hypernatremic dehydration 30 HP:0004906
45 food allergy 30 HP:0500093
46 brittle scalp hair 30 HP:0004779

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Growth Other:
failure to thrive

Immunology:
asthma
recurrent infections
angioedema
food allergy
hay fever
more
Muscle Soft Tissue:
angioedema

Skin Nails Hair Skin Histology:
parakeratosis
psoriasiform epidermal hyperplasia

Neurologic Central Nervous System:
developmental delay

Skin Nails Hair Hair:
sparse eyebrows
sparse, brittle scalp hair
trichorrhexis invaginata ("bamboo hair")

Respiratory Airways:
asthma

Skin Nails Hair Skin:
urticaria
generalized erythroderma
ichthyosis linearis circumflexa
congenital lamellar ichthyosis

Hematology:
hypereosinophilia

Metabolic Features:
hypernatremic dehydration

Head And Neck Eyes:
sparse eyebrows

Abdomen Gastrointestinal:
enteropathy with villous atrophy
intestinal atresia (rare)

Clinical features from OMIM®:

256500 (Updated 08-Dec-2022)

UMLS symptoms related to Netherton Syndrome:


trichorrhexis invaginata

MGI Mouse Phenotypes related to Netherton Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.77 CDSN DSC1 DSG1 ELANE GBA1 KLK14
2 integument MP:0010771 9.28 CDSN DSC1 DSG1 ELANE GBA1 KLK6

Drugs & Therapeutics for Netherton Syndrome

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

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 HIV Protease Inhibitors Phase 2, Phase 3
2 Serine Proteinase Inhibitors Phase 2, Phase 3
3
protease inhibitors Phase 2, Phase 3
4
Serine Investigational, Nutraceutical Phase 2, Phase 3 56-45-1 5951
5
Adalimumab Approved, Experimental Phase 2 331731-18-1
6
Pimecrolimus Approved, Investigational Phase 1, Phase 2 137071-32-0 17753757 6509979
7 Antirheumatic Agents Phase 2
8 Anti-Inflammatory Agents Phase 2
9 Calcineurin Inhibitors Phase 1, Phase 2
10 Anti-Inflammatory Agents, Non-Steroidal Phase 1, Phase 2
11 Analgesics, Non-Narcotic Phase 1, Phase 2
12 Analgesics Phase 1, Phase 2
13 Immunosuppressive Agents Phase 1, Phase 2
14 Dermatologic Agents Phase 1, Phase 2
15 Immunologic Factors Phase 1, Phase 2
16 Immunoglobulins Phase 2
17 Antibodies Phase 2

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 A Randomized Double-blinded Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome Recruiting NCT04244006 Phase 2, Phase 3 Dupilumab Prefilled Syringe
2 A Multicenter, Randomized, Vehicle-Controlled, Double-Blind, Parallel Comparison Study of QRX003 Lotion in Subjects With Netherton Syndrome Recruiting NCT05521438 Phase 2, Phase 3 QRX003-2% Lotion;QRX003-4% Lotion;Vehicle
3 Phase II Clinical Trial Using Humira in Netherton Syndrome Completed NCT02113904 Phase 2 Adalimumab
4 Exploratory Safety and Systemic Absorption of Elidel (Pimecrolimus) 1% Cream for the Treatment of Netherton Syndrome Completed NCT00208026 Phase 1, Phase 2 Pimecrolimus 1% Cream
5 A Multicenter Study With a Randomized, Double-Blind, Placebo-Controlled Period, Followed by an Open-Label Maintenance Dosing Period to Evaluate the Efficacy and Safety of Secukinumab in Patients With Ichthyoses Completed NCT03041038 Phase 2 Secukinumab;Placebo
6 A Phase I/II, Multicenter, Randomized, Double-blind, Placebo Within-patient Controlled, First-in-human (FIH) Proof of Concept (PoC) Study to Evaluate the Safety and Efficacy of Topically Applied SXR1096 Cream in Patients With Netherton Syndrome (NS) Recruiting NCT05211830 Phase 1, Phase 2 SXR1096 cream;Placebo cream
7 Phase I Study of Ex-vivo Lentiviral Gene Therapy for the Inherited Skin Disease Netherton Syndrome Unknown status NCT01545323 Phase 1
8 A First-In-human Study to Evaluate Safety and Tolerability of Topical BPR277 in Healthy Volunteers, and Proof of Concept (PoC) Studies to Evaluate the Safety, Tolerability, and Efficacy of Topical BPR277 in Patients With Atopic Dermatitis and Netherton Syndrome Completed NCT01428297 Phase 1 BPR277 ointment (controlled application);Placebo (Vehicle);BPR277 ointment;BPR277
9 A Phase 1, Subject- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Multiple Ascending Subcutaneous Doses of DS-2325a in Healthy Subjects Recruiting NCT05583669 Phase 1 DS-2325a;Placebo
10 A Phase 1, Subjects- and Investigator-Blinded, Sponsor-Unblinded, Placebo-Controlled, Randomized, Sequential Cohort Study to Assess the Safety and Pharmacokinetics of Single Ascending Subcutaneous and Intravenous Doses of DS-2325a in Healthy Subjects Recruiting NCT05388903 Phase 1 DS-2325a;Placebo
11 Syndrome de Netherton : Aspects Cliniques, Physiopathologiques et Identification de Cibles thérapeutiques Unknown status NCT02081313
12 Defining the Skin and Blood Biomarkers of Ichthyosis Recruiting NCT03417856

Search NIH Clinical Center for Netherton Syndrome

Cochrane evidence based reviews: netherton syndrome

Genetic Tests for Netherton Syndrome

Genetic tests related to Netherton Syndrome:

# Genetic test Affiliating Genes
1 Netherton Syndrome 28 SPINK5

Anatomical Context for Netherton Syndrome

Organs/tissues related to Netherton Syndrome:

MalaCards : Skin, Kidney, Heart, Smooth Muscle, Bone Marrow, Trachea, Endothelial

Publications for Netherton Syndrome

Articles related to Netherton Syndrome:

(show top 50) (show all 760)
# Title Authors PMID Year
1
Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families. 53 62 57 5
11841556 2002
2
A case of Netherton syndrome with intestinal atresia, a novel SPINK5 mutation, and a fatal course. 62 57 5
28832989 2017
3
Is c.1431-12G>A A common European mutation of SPINK5? report of a patient with Netherton Syndrome. 62 57 5
28289593 2016
4
Comèl-Netherton syndrome defined as primary immunodeficiency. 62 57 5
19683336 2009
5
Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. 62 57 5
10835624 2000
6
Corneodesmosomal cadherins are preferential targets of stratum corneum trypsin- and chymotrypsin-like hyperactivity in Netherton syndrome. 53 62 5
16628198 2006
7
Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome. 53 62 5
16601670 2006
8
LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome. 53 62 57
12915442 2003
9
The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis. 53 62 5
11511292 2001
10
Netherton's syndrome: a syndrome of elevated IgE and characteristic skin and hair findings. 53 62 57
7822652 1995
11
A case of Netherton syndrome with mutation in SPINK5 and FLG. 62 57
28943498 2017
12
Netherton Syndrome: A Genotype-Phenotype Review. 62 57
27905021 2017
13
Intrafamily and Interfamilial Phenotype Variation and Immature Immunity in Patients With Netherton Syndrome and Finnish SPINK5 Founder Mutation. 62 5
26865388 2016
14
Betapapillomavirus in multiple non-melanoma skin cancers of Netherton syndrome: Case report and published work review. 62 5
25917539 2015
15
Ichthyosis Linearis Circumflexa as the Only Clinical Manifestation of Netherton Syndrome. 62 5
25710899 2015
16
New mutation leading to the full variety of typical features of the Netherton syndrome. 62 5
26031502 2015
17
Exon-Specific U1s Correct SPINK5 Exon 11 Skipping Caused by a Synonymous Substitution that Affects a Bifunctional Splicing Regulatory Element. 62 5
25665175 2015
18
Transgenic kallikrein 5 mice reproduce major cutaneous and systemic hallmarks of Netherton syndrome. 62 57
24534191 2014
19
Netherton syndrome associated with growth hormone deficiency. 62 5
24015757 2014
20
Lethal Netherton syndrome due to homozygous p.Arg371X mutation in SPINK5. 62 5
23331056 2013
21
A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering exonic splicing regulatory elements. 62 5
22377713 2012
22
Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations. 62 5
22089833 2012
23
Matriptase initiates activation of epidermal pro-kallikrein and disease onset in a mouse model of Netherton syndrome. 62 57
20657595 2010
24
A new SPINK5 donor splice site mutation in siblings with Netherton syndrome. 62 5
20107740 2010
25
Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome. 62 57
15590704 2005
26
Severe hypernatremic dehydration in an infant with Netherton syndrome. 62 57
11693786 2001
27
Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping. 62 57
10712206 2000
28
Altered lamellar body secretion and stratum corneum membrane structure in Netherton syndrome: differentiation from other infantile erythrodermas and pathogenic implications. 62 57
10411158 1999
29
Comèl-Netherton syndrome complicated by papillomatous skin lesions containing human papillomaviruses 51 and 52 and plane warts containing human papillomavirus 16. 62 57
10354085 1999
30
Neterton's syndrome and ichthyosis linearis circumflexa. 62 57
4242601 1969
31
Multiple defects of the hair shaft in Netherton's disease. Association with ichthyosis linearis circumflexa. 62 57
5359904 1969
32
Whole-exome sequencing for diagnosis of hereditary ichthyosis. 5
29444371 2018
33
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. 5
17576681 2007
34
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
35
LEKTI, a novel 15-domain type of human serine proteinase inhibitor. 57
10419450 1999
36
RNA surveillance. Unforeseen consequences for gene expression, inherited genetic disorders and cancer. 57
10098411 1999
37
Statistical features of human exons and their flanking regions. 5
9536098 1998
38
Netherton's syndrome in a male. 57
5170973 1971
39
Netherton's syndrome. 57
5652709 1968
40
Netherton's disease in two sisters. 57
6024735 1967
41
NETHERTON'S DISEASE; TRICHORRHEXIS INVAGINATA (BAMBOO HAIR), CONGENITAL ICHTHYOSIFORM ERYTHRODERMA AND THE ATOPIC DIATHESIS. A HISTOPATHOLOGIC STUDY. 57
14070837 1964
42
A unique case of trichorrhexis nodosa; bamboo hairs. 57
13582191 1958
43
Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing. 53 62
20179351 2010
44
A heterozygous null mutation combined with the G1258A polymorphism of SPINK5 causes impaired LEKTI function and abnormal expression of skin barrier proteins. 53 62
19438860 2009
45
A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population. 53 62
19534795 2009
46
Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients. 53 62
17989726 2008
47
Netherton syndrome: successful use of topical tacrolimus and pimecrolimus in four siblings. 53 62
17343588 2007
48
Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue-engineered skin. 53 62
17223863 2007
49
Proteolytic processing of human growth hormone by multiple tissue kallikreins and regulation by the serine protease inhibitor Kazal-Type5 (SPINK5) protein. 53 62
17140555 2007
50
Netherton syndrome: report of identical twins presenting with severe atopic dermatitis. 53 62
16670861 2006

Variations for Netherton Syndrome

ClinVar genetic disease variations for Netherton Syndrome:

5 (show top 50) (show all 555)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SPINK5 NM_006846.4(SPINK5):c.2368C>T (p.Arg790Ter) SNV Pathogenic
5266 rs121908387 GRCh37: 5:147499626-147499626
GRCh38: 5:148120063-148120063
2 SPINK5 NM_006846.4(SPINK5):c.283-2A>T SNV Pathogenic
5267 rs587777749 GRCh37: 5:147465966-147465966
GRCh38: 5:148086403-148086403
3 SPINK5 NM_006846.4(SPINK5):c.652C>T (p.Arg218Ter) SNV Pathogenic
351517 rs199757347 GRCh37: 5:147470777-147470777
GRCh38: 5:148091214-148091214
4 SPINK5 NM_006846.4(SPINK5):c.238dup (p.Ala80fs) DUP Pathogenic
459573 rs752179828 GRCh37: 5:147451736-147451737
GRCh38: 5:148072173-148072174
5 SPINK5 NM_006846.4(SPINK5):c.354_357del (p.Cys119fs) DEL Pathogenic
625164 rs1561680487 GRCh37: 5:147466036-147466039
GRCh38: 5:148086473-148086476
6 SPINK5 NM_006846.4(SPINK5):c.995del (p.Met332fs) DEL Pathogenic
625167 rs1561686960 GRCh37: 5:147477542-147477542
GRCh38: 5:148097979-148097979
7 SPINK5 NM_006846.4(SPINK5):c.355_371delinsGACAACATATGACAACAGATGAC (p.Cys119_Lys124delinsAspAsnIleTer) INDEL Pathogenic
661320 rs1581064755 GRCh37: 5:147466040-147466056
GRCh38: 5:148086477-148086493
8 SPINK5 NM_006846.4(SPINK5):c.2671C>T (p.Arg891Ter) SNV Pathogenic
852460 rs749828824 GRCh37: 5:147504332-147504332
GRCh38: 5:148124769-148124769
9 SPINK5 NM_006846.4(SPINK5):c.882+1_882+3del MICROSAT Pathogenic
1012378 rs750225476 GRCh37: 5:147475466-147475468
GRCh38: 5:148095903-148095905
10 SPINK5 NM_006846.4(SPINK5):c.2240+1G>A SNV Pathogenic
372517 rs775341740 GRCh37: 5:147498128-147498128
GRCh38: 5:148118565-148118565
11 SPINK5 NC_000005.9:g.(?_147443360)_(147484583_?)del DEL Pathogenic
1072829 GRCh37: 5:147443360-147484583
GRCh38:
12 SPINK5 NM_006846.4(SPINK5):c.2472del (p.Glu825fs) DEL Pathogenic
1376783 GRCh37: 5:147499886-147499886
GRCh38: 5:148120323-148120323
13 SPINK5 NM_006846.4(SPINK5):c.679G>T (p.Glu227Ter) SNV Pathogenic
1423328 GRCh37: 5:147473929-147473929
GRCh38: 5:148094366-148094366
14 SPINK5 NM_006846.4(SPINK5):c.2989C>T (p.Arg997Ter) SNV Pathogenic
1422122 GRCh37: 5:147510846-147510846
GRCh38: 5:148131283-148131283
15 SPINK5 NC_000005.9:g.(?_147443608)_(147451803_?)del DEL Pathogenic
1456239 GRCh37: 5:147443608-147451803
GRCh38:
16 SPINK5 NM_006846.4(SPINK5):c.1242_1246del (p.Lys415fs) MICROSAT Pathogenic
1460134 GRCh37: 5:147480932-147480936
GRCh38: 5:148101369-148101373
17 SPINK5 NM_006846.4(SPINK5):c.2953_2954del (p.Phe985fs) DEL Pathogenic
1448931 GRCh37: 5:147506630-147506631
GRCh38: 5:148127067-148127068
18 SPINK5 NM_006846.4(SPINK5):c.1233del (p.Glu412fs) DEL Pathogenic
1452231 GRCh37: 5:147480929-147480929
GRCh38: 5:148101366-148101366
19 SPINK5 NM_006846.4(SPINK5):c.2758C>T (p.Arg920Ter) SNV Pathogenic
1350963 GRCh37: 5:147505304-147505304
GRCh38: 5:148125741-148125741
20 SPINK5 NM_006846.4(SPINK5):c.2038_2039del (p.Lys680fs) DEL Pathogenic
1072025 GRCh37: 5:147495954-147495955
GRCh38: 5:148116391-148116392
21 SPINK5 NM_006846.4(SPINK5):c.1437del (p.Glu480fs) DEL Pathogenic
529155 rs1554104853 GRCh37: 5:147484520-147484520
GRCh38: 5:148104957-148104957
22 SPINK5 NM_006846.4(SPINK5):c.1012C>T (p.Gln338Ter) SNV Pathogenic
835174 rs1394583450 GRCh37: 5:147478798-147478798
GRCh38: 5:148099235-148099235
23 SPINK5 NM_006846.4(SPINK5):c.1825C>T (p.Gln609Ter) SNV Pathogenic
843075 rs1366194827 GRCh37: 5:147492435-147492435
GRCh38: 5:148112872-148112872
24 SPINK5 NM_006846.4(SPINK5):c.2611C>T (p.Arg871Ter) SNV Pathogenic
959534 rs1340491788 GRCh37: 5:147503468-147503468
GRCh38: 5:148123905-148123905
25 SPINK5 NM_006846.4(SPINK5):c.67A>T (p.Lys23Ter) SNV Pathogenic
969619 rs1482249008 GRCh37: 5:147444921-147444921
GRCh38: 5:148065358-148065358
26 SPINK5 NM_006846.4(SPINK5):c.850del (p.Glu284fs) DEL Pathogenic
639460 rs1581074967 GRCh37: 5:147475436-147475436
GRCh38: 5:148095873-148095873
27 SPINK5 NM_006846.4(SPINK5):c.1915_1916del (p.Leu639fs) DEL Pathogenic
645505 rs1581096271 GRCh37: 5:147493950-147493951
GRCh38: 5:148114387-148114388
28 SPINK5 NM_006846.4(SPINK5):c.1089T>G (p.Tyr363Ter) SNV Pathogenic
646119 rs752777832 GRCh37: 5:147478875-147478875
GRCh38: 5:148099312-148099312
29 SPINK5 NM_006846.4(SPINK5):c.374del (p.Thr125fs) DEL Pathogenic
654217 rs1419297868 GRCh37: 5:147466059-147466059
GRCh38: 5:148086496-148086496
30 SPINK5 NM_006846.4(SPINK5):c.1888-1G>A SNV Pathogenic
654917 rs759255682 GRCh37: 5:147493924-147493924
GRCh38: 5:148114361-148114361
31 SPINK5 NM_006846.4(SPINK5):c.690del (p.Lys230fs) DEL Pathogenic
570884 rs1561684604 GRCh37: 5:147473936-147473936
GRCh38: 5:148094373-148094373
32 SPINK5 NM_006846.4(SPINK5):c.2468dup (p.Lys824fs) DUP Pathogenic
5268 rs565782662 GRCh37: 5:147499874-147499875
GRCh38: 5:148120311-148120312
33 SPINK5 NM_006846.4(SPINK5):c.81+2T>A SNV Pathogenic
429608 rs1131691490 GRCh37: 5:147444937-147444937
GRCh38: 5:148065374-148065374
34 SPINK5 NM_006846.4(SPINK5):c.2579del (p.Lys860fs) DEL Pathogenic
664791 rs1362009010 GRCh37: 5:147503434-147503434
GRCh38: 5:148123871-148123871
35 SPINK5 NM_006846.4(SPINK5):c.2468del (p.Lys823fs) DEL Pathogenic
523932 rs565782662 GRCh37: 5:147499875-147499875
GRCh38: 5:148120312-148120312
36 SPINK5 NM_006846.4(SPINK5):c.316_317del (p.Asp106fs) MICROSAT Pathogenic
938196 rs763649250 GRCh37: 5:147465998-147465999
GRCh38: 5:148086435-148086436
37 SPINK5 NM_006846.4(SPINK5):c.1000C>T (p.Gln334Ter) SNV Pathogenic
956463 rs924297783 GRCh37: 5:147477547-147477547
GRCh38: 5:148097984-148097984
38 SPINK5 NM_006846.4(SPINK5):c.1048C>T (p.Arg350Ter) SNV Pathogenic
449101 rs373463881 GRCh37: 5:147478834-147478834
GRCh38: 5:148099271-148099271
39 SPINK5 NM_006846.4(SPINK5):c.1111C>T (p.Arg371Ter) SNV Pathogenic
989374 rs777436361 GRCh37: 5:147480035-147480035
GRCh38: 5:148100472-148100472
40 SPINK5 NM_006846.4(SPINK5):c.2260A>T (p.Lys754Ter) SNV Pathogenic
1379542 GRCh37: 5:147498568-147498568
GRCh38: 5:148119005-148119005
41 SPINK5 NM_006846.4(SPINK5):c.1732C>T (p.Arg578Ter) SNV Pathogenic
1456666 GRCh37: 5:147491370-147491370
GRCh38: 5:148111807-148111807
42 SPINK5 NM_006846.4(SPINK5):c.649C>T (p.Arg217Ter) SNV Pathogenic
523773 rs367958902 GRCh37: 5:147470774-147470774
GRCh38: 5:148091211-148091211
43 SPINK5 NM_006846.4(SPINK5):c.1816_1820+21delinsCT INDEL Pathogenic
625166 rs1561695740 GRCh37: 5:147491454-147491479
GRCh38: 5:148111891-148111916
44 SPINK5 NM_006846.4(SPINK5):c.1302+4A>T SNV Pathogenic
279898 rs201269335 GRCh37: 5:147481003-147481003
GRCh38: 5:148101440-148101440
45 SPINK5 NM_006846.4(SPINK5):c.2557C>T (p.Arg853Ter) SNV Pathogenic
623372 rs753621591 GRCh37: 5:147503414-147503414
GRCh38: 5:148123851-148123851
46 SPINK5 NM_006846.4(SPINK5):c.2264dup (p.Asn755fs) DUP Pathogenic
279899 rs748978134 GRCh37: 5:147498566-147498567
GRCh38: 5:148119003-148119004
47 SPINK5 NM_006846.4(SPINK5):c.1431-12G>A SNV Pathogenic/Likely Pathogenic
372516 rs368134354 GRCh37: 5:147484503-147484503
GRCh38: 5:148104940-148104940
48 SPINK5 NM_006846.4(SPINK5):c.891C>T (p.Cys297=) SNV Pathogenic/Likely Pathogenic
374066 rs752941297 GRCh37: 5:147477438-147477438
GRCh38: 5:148097875-148097875
49 SPINK5 NM_006846.4(SPINK5):c.2423C>T (p.Thr808Ile) SNV Likely Pathogenic
848986 rs1212676320 GRCh37: 5:147499681-147499681
GRCh38: 5:148120118-148120118
50 SPINK5 NM_006846.4(SPINK5):c.81+5G>A SNV Likely Pathogenic
835648 rs771730802 GRCh37: 5:147444940-147444940
GRCh38: 5:148065377-148065377

Expression for Netherton Syndrome

Search GEO for disease gene expression data for Netherton Syndrome.

Pathways for Netherton Syndrome

GO Terms for Netherton Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 10.34 CELA2A CTRL CTSG ELANE GBA1 IGHE
2 extracellular region GO:0005576 10.34 CDSN CELA2A CTSG DCD ELANE IGHE
3 desmosome GO:0030057 9.77 DSG1 DSC1 CDSN
4 secretory granule GO:0030141 9.73 CTSG ELANE KLK14 KLK5 KLK6 KLK7
5 keratohyalin granule GO:0036457 9.71 FLG CELA2A
6 epidermal lamellar body GO:0097209 9.63 SPINK5 KLK7 KLK5
7 cornified envelope GO:0001533 9.5 TGM1 PI3 KLK7 KLK6 FLG DSG1

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

# Name GO ID Score Top Affiliating Genes
1 keratinocyte differentiation GO:0030216 9.87 TGM3 TGM1 FLG CDSN
2 defense response to fungus GO:0050832 9.83 ELANE DCD CTSG
3 skin morphogenesis GO:0043589 9.76 GBA1 CDSN
4 extracellular matrix disassembly GO:0022617 9.76 CTSG ELANE KLK5 KLK7
5 positive regulation of G protein-coupled receptor signaling pathway GO:0045745 9.73 KLK6 KLK5 KLK14
6 positive regulation of antibacterial peptide production GO:0002803 9.71 KLK7 KLK5
7 cell envelope organization GO:0043163 9.67 TGM3 TGM1
8 peptide cross-linking GO:0018149 9.56 TGM3 TGM1 PI3 FLG
9 proteolysis GO:0006508 9.55 KLK7 KLK6 KLK5 KLK14 ELANE DCD

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

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 10 KLK7 KLK6 KLK5 KLK14 ELANE DCD
2 hydrolase activity GO:0016787 9.96 KLK7 KLK6 KLK5 KLK14 GBA1 ELANE
3 serine-type endopeptidase activity GO:0004252 9.86 CELA2A CTRL CTSG ELANE KLK14 KLK5
4 protein-glutamine gamma-glutamyltransferase activity GO:0003810 9.62 TGM3 TGM1
5 serine-type peptidase activity GO:0008236 9.4 KLK7 KLK6 KLK5 KLK14 ELANE CTSG

Sources for Netherton Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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