MEDNIK
MCID: MNT317
MIFTS: 45

Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma (MEDNIK)

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

Aliases & Classifications for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

MalaCards integrated aliases for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

Name: Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma 57 73 29 6
Mednik Syndrome 57 12 74 58 36 13 15
Erythrokeratodermia Variabilis 3 57 12 73 71
Erythrokeratodermia Variabilis, Kamouraska Type 57 12
Mednik 57 73
Ekv3 57 73
Intellectual Disability-Enteropathy-Hearing Loss-Peripheral Neuropathy-Ichthyosis-Keratodermia Syndrome 58
Intellectual Disability-Enteropathy-Deafness-Peripheral Neuropathy-Ichthyosis-Keratodermia Syndrome 58
Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, Keratoderma 39
Mental Retardation, Enteropathy, Deafness, Neuropathy, Ichthyosis, Keratodermia 12
Erythrokeratodermia Variabilis Kamouraska Type 73
Erythrokeratodermia Variabilis 3; Ekv3 57

Characteristics:

Orphanet epidemiological data:

58
mednik syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide);

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
may result in early death from severe diarrhea
prevalent in quebec


HPO:

31
mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma:
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare otorhinolaryngological diseases
Rare skin diseases
Inborn errors of metabolism
Developmental anomalies during embryogenesis


Summaries for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

KEGG : 36 MEDNIK syndrome (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratodermia) is a rare autosomal recessive neurocutaneous disease. MEDNIK syndrome is caused by AP1S1 gene mutations, encoding the subunit of the AP-1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans-Golgi network, endosomes and the plasma membrane.

MalaCards based summary : Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma, also known as mednik syndrome, is related to disorder of copper metabolism and menkes disease, and has symptoms including diarrhea An important gene associated with Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma is AP1S1 (Adaptor Related Protein Complex 1 Subunit Sigma 1), and among its related pathways/superpathways are Lysosome and Innate Immune System. Affiliated tissues include spinal cord, liver and skin, and related phenotypes are intellectual disability and ichthyosis

Disease Ontology : 12 A syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma. It is cause by homozygous mutation in the AP1S1 gene on chromosome 7q22.

OMIM® : 57 MEDNIK is a severe multisystem disorder characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma. It shows phenotypic similarities to CEDNIK (609528) (summary by Montpetit et al., 2008). (609313) (Updated 05-Mar-2021)

UniProtKB/Swiss-Prot : 73 Mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma: A disorder characterized by erythematous skin lesions and hyperkeratosis, severe psychomotor retardation, peripheral neuropathy, sensorineural hearing loss, together with elevated very-long-chain fatty acids and severe congenital diarrhea.

Wikipedia : 74 MEDNIK syndrome (OMIM 609313), also known as "syndrome de Kamouraska" (syndrome from Kamouraska), is a... more...

Related Diseases for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Diseases related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 33)
# Related Disease Score Top Affiliating Genes
1 disorder of copper metabolism 30.3 ATP7B ATP7A
2 menkes disease 30.0 PAM ATP7B ATP7A
3 aceruloplasminemia 29.9 SLC33A1 ATP7B ATP7A
4 ichthyosis 29.9 SNAP29 ELOVL4 AP1S1 AP1B1
5 hypermanganesemia with dystonia 10.3 SLC33A1 AP1S1
6 hypermanganesemia with dystonia 2 10.3 SLC33A1 AP1S1
7 cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome 10.1 SNAP29 AP1S1
8 branchiootic syndrome 1 10.1
9 hypotrichosis-deafness syndrome 10.1 GJB4 GJB3
10 hemochromatosis, type 5 10.1 SLC33A1 AP5M1 AP1S1
11 pseudoainhum 10.1 GJB4 GJB3
12 hereditary lymphedema ic 10.1 GJB4 GJB3
13 erythrokeratoderma 10.1 GJB4 GJB3
14 occipital horn syndrome 10.1 PAM ATP7B ATP7A AP1S1
15 knuckle pads 10.1 GJB4 GJB3
16 deafness, autosomal dominant 3a 10.0 GJB4 GJB3
17 keratoderma, palmoplantar, with deafness 10.0 GJB4 GJB3
18 leukodystrophy, hypomyelinating, 2 10.0 SNAP29 GJB4
19 peripheral nervous system disease 10.0
20 neuropathy 10.0
21 bart-pumphrey syndrome 10.0 GJB4 GJB3
22 palmoplantar keratoderma and congenital alopecia 1 10.0 GJB4 GJB3
23 spinal muscular atrophy, distal, x-linked 3 9.9 SLC33A1 PAM ATP7B ATP7A AP1S1
24 keratitis-ichthyosis-deafness syndrome, autosomal dominant 9.9
25 keratitis-ichthyosis-deafness syndrome, autosomal recessive 9.9
26 wilson disease 9.9
27 alacrima, achalasia, and mental retardation syndrome 9.9
28 autosomal recessive disease 9.9
29 cholestasis 9.9
30 clouston syndrome 9.9 GJB4 GJB3
31 pettigrew syndrome 9.9 PAM AP1S2 AP1S1 AP1M2 AP1M1
32 oculodentodigital dysplasia 9.8 GJB4 GJB3
33 erythrokeratodermia variabilis et progressiva 1 9.4 SNAP29 GJB4 GJB3 ELOVL4 AP1S1

Graphical network of the top 20 diseases related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:



Diseases related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma

Symptoms & Phenotypes for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Human phenotypes related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

58 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 ichthyosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0008064
3 hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000962
4 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
5 abnormal intestine morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0002242
6 decreased circulating copper concentration 58 31 frequent (33%) Frequent (79-30%) HP:0011967
7 intrahepatic cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001406
8 decreased circulating ceruloplasmin concentration 31 frequent (33%) HP:0010837
9 cataract 31 occasional (7.5%) HP:0000518
10 hearing impairment 31 HP:0000365
11 global developmental delay 31 HP:0001263
12 growth delay 31 HP:0001510
13 hepatic fibrosis 31 HP:0001395
14 cirrhosis 31 HP:0001394
15 upslanted palpebral fissure 31 HP:0000582
16 high forehead 31 HP:0000348
17 erythema 31 HP:0010783
18 cholestasis 31 HP:0001396
19 diarrhea 31 HP:0002014
20 generalized hypotonia 31 HP:0001290
21 decreased serum ceruloplasmin 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skin Nails Hair Skin:
ichthyosis
erythema

Head And Neck Head:
high forehead

Abdomen Gastrointestinal:
diarrhea
enteropathy

Neurologic Central Nervous System:
hypotonia
mental retardation
delayed psychomotor development

Head And Neck Eyes:
upslanting palpebral fissures
cataracts (uncommon)

Laboratory Abnormalities:
increased very-long chain fatty acids

Abdomen Liver:
hepatic fibrosis
cirrhosis
cholestasis

Neurologic Peripheral Nervous System:
peripheral neuropathy

Muscle Soft Tissue:
hypotonia

Growth Other:
growth retardation

Head And Neck Ears:
deafness, sensorineural, congenital

Clinical features from OMIM®:

609313 (Updated 05-Mar-2021)

UMLS symptoms related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:


diarrhea

GenomeRNAi Phenotypes related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell size GR00098-A-4 8.8 AP1G1 PAM VPS35L

MGI Mouse Phenotypes related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.73 AP1B1 AP1G1 AP1M2 AP1S2 ATP7A ATP7B
2 integument MP:0010771 9.23 AP1S2 AP5M1 ATP7A ATP7B ELOVL4 GJB3

Drugs & Therapeutics for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Search Clinical Trials , NIH Clinical Center for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma

Genetic Tests for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Genetic tests related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

# Genetic test Affiliating Genes
1 Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma 29 AP1S1

Anatomical Context for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

MalaCards organs/tissues related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

40
Spinal Cord, Liver, Skin

Publications for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Articles related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

(show all 17)
# Title Authors PMID Year
1
MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features. 6 61 57
30244301 2018
2
MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. 57 6 61
23423674 2013
3
Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord. 6 57 61
19057675 2008
4
An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22. 57
15668823 2005
5
Atypical erythrokeratoderma with deafness, physical retardation and peripheral neuropathy. 57
4342731 1972
6
AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect. 61
32306098 2020
7
Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice? 61
32613181 2020
8
Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome. 61
31630791 2019
9
Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. 61
30965071 2019
10
Classification and differential diagnosis of Wilson's disease. 61
31179300 2019
11
Neuro-ichthyotic Syndromes: A Case Series. 61
29899769 2018
12
Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells. 61
29127151 2017
13
Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme. 61
26170456 2015
14
Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1. 61
25378584 2015
15
AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. 61
24754424 2014
16
Inborn errors of copper metabolism. 61
23622398 2013
17
Banding pattern on polarized hair microscopic examination and unilateral polymicrogyria in a patient with steroid sulfatase deficiency. 61
21931015 2012

Variations for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

ClinVar genetic disease variations for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AP1S1 NM_001283.5(AP1S1):c.183-2A>G SNV Pathogenic 39854 rs751430853 7:100800656-100800656 7:101157375-101157375
2 AP1S1 NM_001283.5(AP1S1):c.364dup (p.Asp122fs) Duplication Pathogenic 503720 rs767358930 7:100802404-100802405 7:101159123-101159124
3 AP1S1 NM_001283.5(AP1S1):c.220C>T (p.Gln74Ter) SNV Likely pathogenic 804403 rs1584203922 7:100800695-100800695 7:101157414-101157414
4 AP1S1 NM_001283.5(AP1S1):c.364del (p.Asp122fs) Deletion Likely pathogenic 804404 rs767358930 7:100802405-100802405 7:101159124-101159124

Expression for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Search GEO for disease gene expression data for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma.

Pathways for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Pathways related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to KEGG:

36
# Name Kegg Source Accession
1 Lysosome hsa04142

Pathways related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to GeneCards Suite gene sharing:

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.77 VPS35L SNAP29 ATP7A AP1S3 AP1S2 AP1S1
2
Show member pathways
13.21 SNAP29 GJB4 GJB3 AP1S3 AP1S2 AP1S1
3
Show member pathways
13.18 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
4
Show member pathways
12.78 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
5
Show member pathways
12.34 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
6
Show member pathways
12.24 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
7 11.91 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
8 11.71 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
9
Show member pathways
11.45 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
10 11.02 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
11 10.96 ATP7B ATP7A

GO Terms for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

Cellular components related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.45 VPS35L TMCO4 SNAP29 SLC33A1 PAM GJB4
2 Golgi apparatus GO:0005794 10.1 SNAP29 ATP7B ATP7A AP1S3 AP1S2 AP1S1
3 intracellular membrane-bounded organelle GO:0043231 10.09 GJB3 CCDC93 AP1S3 AP1S2 AP1S1 AP1M2
4 cytoplasmic vesicle GO:0031410 10.07 SNAP29 PAM ATP7B AP1S3 AP1S2 AP1S1
5 lysosomal membrane GO:0005765 9.92 AP5M1 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1
6 clathrin-coated vesicle membrane GO:0030665 9.78 AP1M2 AP1M1 AP1G1 AP1B1
7 late endosome GO:0005770 9.74 ATP7B ATP7A AP5M1
8 clathrin-coated vesicle GO:0030136 9.72 AP1M2 AP1M1 AP1G1
9 clathrin-coated pit GO:0005905 9.71 AP1S3 AP1S2 AP1S1
10 cytoplasmic vesicle membrane GO:0030659 9.7 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
11 membrane coat GO:0030117 9.65 AP1S3 AP1S2 AP1S1 AP1G1 AP1B1
12 Golgi membrane GO:0000139 9.65 SNAP29 SLC33A1 ATP7B AP1S3 AP1S2 AP1S1
13 clathrin adaptor complex GO:0030131 9.63 AP1M2 AP1M1 AP1B1
14 connexin complex GO:0005922 9.56 GJB4 GJB3
15 AP-1 adaptor complex GO:0030121 9.52 AP1S1 AP1G1
16 AP-type membrane coat adaptor complex GO:0030119 9.51 AP5M1 AP1S2
17 trans-Golgi network membrane GO:0032588 9.23 ATP7B AP1S3 AP1S2 AP1S1 AP1M2 AP1M1

Biological processes related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 intracellular protein transport GO:0006886 9.87 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
2 vesicle-mediated transport GO:0016192 9.8 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
3 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 9.7 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1
4 protein transport GO:0015031 9.7 VPS35L SNAP29 CCDC93 AP5M1 AP1S3 AP1S2
5 Golgi to plasma membrane transport GO:0006893 9.57 VPS35L CCDC93
6 melanosome organization GO:0032438 9.56 AP1M1 AP1G1
7 retrograde transport, endosome to plasma membrane GO:1990126 9.55 VPS35L CCDC93
8 inorganic cation transmembrane transport GO:0098662 9.54 ATP7B ATP7A
9 response to copper ion GO:0046688 9.54 PAM ATP7B ATP7A
10 copper ion transport GO:0006825 9.52 ATP7B ATP7A
11 cellular copper ion homeostasis GO:0006878 9.51 ATP7B ATP7A
12 endosome to melanosome transport GO:0035646 9.49 AP1M1 AP1G1
13 vesicle targeting GO:0006903 9.48 SNAP29 AP1M2
14 copper ion import GO:0015677 9.46 ATP7B ATP7A
15 divalent inorganic cation transport GO:0072511 9.43 ATP7B ATP7A
16 copper ion export GO:0060003 9.4 ATP7B ATP7A
17 regulation of defense response to virus by virus GO:0050690 9.17 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1G1

Molecular functions related to Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 copper ion binding GO:0005507 9.43 PAM ATP7B ATP7A
2 gap junction channel activity GO:0005243 9.37 GJB4 GJB3
3 cation-transporting ATPase activity GO:0019829 9.32 ATP7B ATP7A
4 copper ion transmembrane transporter activity GO:0005375 9.16 ATP7B ATP7A
5 copper-transporting ATPase activity GO:0043682 8.96 ATP7B ATP7A
6 clathrin adaptor activity GO:0035615 8.8 AP1M2 AP1M1 AP1G1

Sources for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy,...

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 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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