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-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,...

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 intrahepatic cholestasis 58 31 frequent (33%) Frequent (79-30%) HP:0001406
7 decreased serum ceruloplasmin 58 31 frequent (33%) Frequent (79-30%) HP:0010837
8 decreased circulating copper concentration 31 frequent (33%) HP:0011967
9 cataract 31 occasional (7.5%) HP:0000518
10 hearing impairment 31 HP:0000365
11 global developmental delay 31 HP:0001263
12 generalized hypotonia 31 HP:0001290
13 erythema 31 HP:0010783
14 cirrhosis 31 HP:0001394
15 growth delay 31 HP:0001510
16 hepatic fibrosis 31 HP:0001395
17 upslanted palpebral fissure 31 HP:0000582
18 high forehead 31 HP:0000348
19 cholestasis 31 HP:0001396
20 diarrhea 31 HP:0002014
21 hypocupremia 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
ichthyosis
erythema

Abdomen Liver:
cirrhosis
hepatic fibrosis
cholestasis

Abdomen Gastrointestinal:
diarrhea
enteropathy

Muscle Soft Tissue:
hypotonia

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

Growth Other:
growth retardation

Neurologic Central Nervous System:
hypotonia
mental retardation
delayed psychomotor development

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 15)
# Title Authors PMID Year
1
Disruption of AP1S1, causing a novel neurocutaneous syndrome, perturbs development of the skin and spinal cord. 61 56 6
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
Homozygous Loss-of-Function Mutations in AP1B1, Encoding Beta-1 Subunit of Adaptor-Related Protein Complex 1, Cause MEDNIK-like Syndrome. 61
31630791 2019
5
Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. 61
30965071 2019
6
Classification and differential diagnosis of Wilson's disease. 61
31179300 2019
7
MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features. 61
30244301 2018
8
Neuro-ichthyotic Syndromes: A Case Series. 61
29899769 2018
9
Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells. 61
29127151 2017
10
Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme. 61
26170456 2015
11
Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1. 61
25378584 2015
12
AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. 61
24754424 2014
13
MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. 61
23423674 2013
14
Inborn errors of copper metabolism. 61
23622398 2013
15
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
12.91 SNAP29 GJB4 AP1S3 AP1S1 AP1B1
2
Show member pathways
12.03 AP1S3 AP1S1 AP1B1
3
Show member pathways
11.92 AP1S3 AP1S1 AP1B1
4 11.52 AP1S3 AP1S1 AP1B1
5 11.34 AP1S3 AP1S1 AP1B1
6 11.19 ATP7B ATP7A
7
Show member pathways
11.08 AP1S3 AP1S1 AP1B1
8 10.78 ATP7B ATP7A
9 10.65 AP1S3 AP1S1 AP1B1

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:

# Name GO ID Score Top Affiliating Genes
1 Golgi apparatus GO:0005794 9.85 SNAP29 ATP7B ATP7A AP1S3 AP1S1 AP1B1
2 cytoplasmic vesicle GO:0031410 9.72 SNAP29 ATP7B AP1S3 AP1S1 AP1B1
3 cytoplasmic vesicle membrane GO:0030659 9.58 AP1S3 AP1S1 AP1B1
4 lysosomal membrane GO:0005765 9.56 AP5B1 AP1S3 AP1S1 AP1B1
5 Golgi membrane GO:0000139 9.43 SNAP29 SLC33A1 ATP7B AP1S3 AP1S1 AP1B1
6 membrane coat GO:0030117 9.33 AP1S3 AP1S1 AP1B1
7 trans-Golgi network membrane GO:0032588 8.92 ATP7B AP1S3 AP1S1 AP1B1

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

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 vesicle-mediated transport GO:0016192 9.72 AP1S3 AP1S1 AP1B1
2 lactation GO:0007595 9.54 ATP7B ATP7A
3 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 9.54 AP1S3 AP1S1 AP1B1
4 endocytic recycling GO:0032456 9.52 VPS35L CCDC93
5 metal ion transport GO:0030001 9.51 ATP7B ATP7A
6 Golgi to plasma membrane transport GO:0006893 9.49 VPS35L CCDC93
7 retrograde transport, endosome to plasma membrane GO:1990126 9.48 VPS35L CCDC93
8 response to copper ion GO:0046688 9.46 ATP7B ATP7A
9 copper ion transport GO:0006825 9.43 ATP7B ATP7A
10 cellular copper ion homeostasis GO:0006878 9.4 ATP7B ATP7A
11 copper ion import GO:0015677 9.32 ATP7B ATP7A
12 divalent inorganic cation transport GO:0072511 9.26 ATP7B ATP7A
13 protein transport GO:0015031 9.17 VPS35L SNAP29 CCDC93 AP5B1 AP1S3 AP1S1
14 copper ion export GO:0060003 9.16 ATP7B ATP7A
15 regulation of defense response to virus by virus GO:0050690 9.13 AP1S3 AP1S1 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 cation-transporting ATPase activity GO:0019829 9.16 ATP7B ATP7A
2 copper ion transmembrane transporter activity GO:0005375 8.96 ATP7B ATP7A
3 copper-transporting ATPase activity GO:0043682 8.62 ATP7B ATP7A

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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