MEDNIK
MCID: MNT317
MIFTS: 43

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 56 73 29 6
Mednik Syndrome 56 12 74 58 36 29 13 15
Erythrokeratodermia Variabilis 3 56 12 73 71
Erythrokeratodermia Variabilis, Kamouraska Type 56 12
Mednik 56 73
Ekv3 56 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 56

Characteristics:

Orphanet epidemiological data:

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

OMIM:

56
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 ichthyosis, 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 Vesicle-mediated transport. Affiliated tissues include skin, spinal cord and liver, 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 : 56 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)

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 24)
# Related Disease Score Top Affiliating Genes
1 disorder of copper metabolism 30.5 ATP7B ATP7A
2 ichthyosis 30.3 SNAP29 ELOVL4 AP1S1 AP1B1
3 aceruloplasminemia 30.1 SLC33A1 ATP7B ATP7A
4 menkes disease 29.9 PAM ATP7B ATP7A AP1S1
5 branchiootic syndrome 1 10.3
6 peripheral nervous system disease 10.3
7 neuropathy 10.3
8 hypermanganesemia with dystonia 2 10.2 SLC33A1 AP1S1
9 hypermanganesemia with dystonia 10.2 SLC33A1 AP1S1
10 cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome 10.1 SNAP29 AP1S1
11 keratitis-ichthyosis-deafness syndrome, autosomal dominant 10.1
12 keratitis-ichthyosis-deafness syndrome, autosomal recessive 10.1
13 wilson disease 10.1
14 alacrima, achalasia, and mental retardation syndrome 10.1
15 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
16 autosomal recessive disease 10.1
17 cholestasis 10.1
18 hemochromatosis, type 5 10.0 SLC33A1 AP5M1 AP1S1
19 leukodystrophy, hypomyelinating, 2 10.0 SNAP29 GJB4
20 occipital horn syndrome 9.8 PAM ATP7B ATP7A AP1S1
21 pettigrew syndrome 9.7 AP5B1 AP1S2 AP1S1 AP1M2 AP1M1
22 erythrokeratodermia variabilis et progressiva 1 9.7 SNAP29 GJB4 ELOVL4 AP1S1
23 spinal muscular atrophy, distal, x-linked 3 9.6 SLC33A1 PAM ATP7B ATP7A AP1S1
24 cataract 8, multiple types 9.5 TGOLN2 AP1M1

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 20)
# 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 peripheral neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009830
4 hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000962
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 decreased serum ceruloplasmin 58 31 frequent (33%) Frequent (79-30%) HP:0010837
8 intrahepatic cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001406
9 cataract 31 occasional (7.5%) HP:0000518
10 hearing impairment 31 HP:0000365
11 global developmental delay 31 HP:0001263
12 erythema 31 HP:0010783
13 cirrhosis 31 HP:0001394
14 growth delay 31 HP:0001510
15 hepatic fibrosis 31 HP:0001395
16 upslanted palpebral fissure 31 HP:0000582
17 high forehead 31 HP:0000348
18 cholestasis 31 HP:0001396
19 diarrhea 31 HP:0002014
20 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
ichthyosis
erythema

Abdomen Liver:
cirrhosis
hepatic fibrosis
cholestasis

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

Neurologic Peripheral Nervous System:
peripheral neuropathy

Head And Neck Head:
high forehead

Muscle Soft Tissue:
hypotonia

Growth Other:
growth retardation

Head And Neck Ears:
deafness, sensorineural, congenital

Clinical features from OMIM:

609313

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


diarrhea

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
2 Mednik Syndrome 29

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

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

40
Skin, Spinal Cord, Liver

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

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

(show all 16)
# Title Authors PMID Year
1
Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord. 6 56 61
19057675 2008
2
An atypical form of erythrokeratodermia variabilis maps to chromosome 7q22. 56
15668823 2005
3
Atypical erythrokeratoderma with deafness, physical retardation and peripheral neuropathy. 56
4342731 1972
4
AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect. 61
32306098 2020
5
Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome. 61
31630791 2019
6
Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. 61
30965071 2019
7
Classification and differential diagnosis of Wilson's disease. 61
31179300 2019
8
MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features. 61
30244301 2018
9
Neuro-ichthyotic Syndromes: A Case Series. 61
29899769 2018
10
Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells. 61
29127151 2017
11
Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme. 61
26170456 2015
12
Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1. 61
25378584 2015
13
AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. 61
24754424 2014
14
MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. 61
23423674 2013
15
Inborn errors of copper metabolism. 61
23622398 2013
16
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>GSNV Pathogenic 39854 rs751430853 7:100800656-100800656 7:101157375-101157375
2 AP1S1 NM_001283.5(AP1S1):c.220C>T (p.Gln74Ter)SNV Likely pathogenic 804403 7:100800695-100800695 7:101157414-101157414
3 AP1S1 NM_001283.5(AP1S1):c.364del (p.Asp122fs)deletion Likely pathogenic 804404 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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.16 TGOLN2 SNAP29 GJB4 AP1S3 AP1S2 AP1S1
2
Show member pathways
12.71 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
3
Show member pathways
12.27 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
4
Show member pathways
12.18 TGOLN2 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1
5 11.91 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
6 11.65 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
7
Show member pathways
11.38 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
8 10.95 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
9 10.92 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 10.42 VPS35L TMCO4 TGOLN2 SNAP29 SLC33A1 PAM
2 Golgi apparatus GO:0005794 10.1 TGOLN2 SNAP29 ATP7B ATP7A AP1S3 AP1S2
3 intracellular membrane-bounded organelle GO:0043231 10.05 CCDC93 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1
4 endosome GO:0005768 9.96 VPS35L TGOLN2 CCDC93 ATP7B AP5M1
5 cytoplasmic vesicle GO:0031410 9.91 SNAP29 PAM ATP7B AP1S3 AP1S2 AP1S1
6 trans-Golgi network GO:0005802 9.83 TGOLN2 PAM ATP7B ATP7A
7 Golgi membrane GO:0000139 9.81 SNAP29 SLC33A1 ATP7B AP1S3 AP1S2 AP1S1
8 cytoplasmic vesicle membrane GO:0030659 9.8 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
9 clathrin-coated vesicle membrane GO:0030665 9.78 TGOLN2 AP1M2 AP1M1 AP1B1
10 late endosome GO:0005770 9.74 ATP7B ATP7A AP5M1
11 clathrin-coated pit GO:0005905 9.71 AP1S3 AP1S2 AP1S1
12 membrane coat GO:0030117 9.67 AP1S3 AP1S2 AP1S1 AP1B1
13 clathrin adaptor complex GO:0030131 9.63 AP1M2 AP1M1 AP1B1
14 AP-type membrane coat adaptor complex GO:0030119 9.61 AP5M1 AP5B1 AP1S2
15 lysosomal membrane GO:0005765 9.56 AP5M1 AP5B1 AP1S3 AP1S2 AP1S1 AP1M2
16 trans-Golgi network transport vesicle GO:0030140 9.55 TGOLN2 ATP7A
17 trans-Golgi network membrane GO:0032588 9.17 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 9.8 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
2 vesicle-mediated transport GO:0016192 9.73 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
3 protein transport GO:0015031 9.7 VPS35L SNAP29 CCDC93 AP5M1 AP5B1 AP1S3
4 lactation GO:0007595 9.63 PAM ATP7B ATP7A
5 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 9.63 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1
6 response to zinc ion GO:0010043 9.57 PAM ATP7A
7 metal ion transport GO:0030001 9.56 ATP7B ATP7A
8 Golgi to plasma membrane transport GO:0006893 9.55 VPS35L CCDC93
9 retrograde transport, endosome to plasma membrane GO:1990126 9.54 VPS35L CCDC93
10 response to copper ion GO:0046688 9.54 PAM ATP7B ATP7A
11 copper ion transport GO:0006825 9.52 ATP7B ATP7A
12 cellular copper ion homeostasis GO:0006878 9.51 ATP7B ATP7A
13 vesicle targeting GO:0006903 9.49 SNAP29 AP1M2
14 copper ion import GO:0015677 9.48 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 9.1 AP1S3 AP1S2 AP1S1 AP1M2 AP1M1 AP1B1

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 9.33 PAM ATP7B ATP7A
2 cation-transporting ATPase activity GO:0019829 9.32 ATP7B ATP7A
3 clathrin adaptor activity GO:0035615 9.26 AP1M2 AP1M1
4 copper ion transmembrane transporter activity GO:0005375 8.96 ATP7B ATP7A
5 copper-transporting ATPase activity GO:0043682 8.62 ATP7B ATP7A

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

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