WRS
MCID: EPP024
MIFTS: 48

Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus (WRS)

Categories: Bone diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

MalaCards integrated aliases for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

Name: Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus 58
Wolcott-Rallison Syndrome 58 12 77 60 76 38 13 56 45 15 41 74
Med-Iddm Syndrome 58 54 76
Iddm-Med Syndrome 58 54 76
Wrs 60 76
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 54
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 60
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 76
Wolcott Rallison Syndrome 54

Characteristics:

Orphanet epidemiological data:

60
wolcott-rallison syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset of diabetes in neonatal period/ early infancy
onset of epiphyseal dysplasia and growth retardation in first 2 years of life


HPO:

33
epiphyseal dysplasia, multiple, with early-onset diabetes mellitus:
Clinical modifier death in infancy
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1667Disease definitionWolcott-Rallison syndrome (WRS) is a very rare genetic disease, characterized by permanent neonatal diabetes mellitus (PNDM) with multiple epiphyseal dysplasia and other clinical manifestations, including recurrent episodes of acute liver failure.EpidemiologyFewer than 60 cases have been reported to date. Most patients are from consanguineous families. Prevalence may therefore vary significantly between countries.WRS may be underdiagnosed because of early death before diagnosis.Clinical descriptionDiabetes occurs early, generally before six months of age, is permanent and insulin-dependent from the onset. Skeletal dysplasia generally manifests within the 1st or 2nd year of life, and is associated with short stature (dwarfism with short trunk). Deficient mineralization or dysplastic changes, affecting the long bones, pelvis and vertebrae, but usually not the skull, may be seen on radiography as early as diabetes onset. Hepatic dysfunction is a 3rd characteristic feature and the most life-threatening complication, and manifests by elevated hepatic enzymes, liver enlargement and recurrent acute liver failure. Other manifestations vary between patients in type and severity and include renal dysfunction, exocrine pancreas insufficiency, intellectual deficit, hypothyroidism, neutropenia and recurrent infections. Clinical course is variable, including within the same sibship.EtiologyWRS is caused by mutations in the EIF2AK3 gene encoding eukaryotic translation initiation factor 2-alpha kinase 3 (PKR-like endoplasmic reticulum kinase; PERK), which plays a key role in translation control during unfolded protein response.Diagnostic methodsDiagnosis should be suspected in any infant with permanent neonatal diabetes and skeletal dysplasia and/or episodes of acute liver failure, and family history of consanguinity and/or neonatal diabetes. Diabetes is not autoimmune as shown by absence of antibodies specific for type 1 diabetes. Radiographs show early signs of multiple epiphyseal dysplasia and deficient mineralization. Molecular genetic testing confirms the diagnosis.Differential diagnosisDifferential diagnosis is based on clinical presentation and, ultimately, genetic testing. That of NDM (see this term) includes transient NDM, and other PNDMs that may be isolated or syndromic. Differential diagnosis of skeletal dysplasia includes other spondylo-epiphyseal dysplasias such as mucopolysaccharidoses (see these terms) where diabetes may occur independently at an older age.Antenatal diagnosisAntenatal diagnosis should be offered to parents of a WRS patient with confirmed EIF2AK3 mutation.Genetic counselingInheritance is autosomal recessive and genetic counseling is possible.Management and treatmentClose therapeutic monitoring of diabetes should be considered and treatment with an insulin pump is recommended, especially in the first months of life, due to the risk of acute episodes of hypoglycemia. At any age, hypoglycemia should be prevented because the disease can decompensate, even if this requires maintaining the level of glucose above the objectives generally recommended in diabetic children. General anesthesia increases the risk of acute aggravation, because of particular sensitivity of patients to anesthetics, and should be avoided wherever possible. Any drug or vaccine not strictly necessary should be limited, due to the risk of triggering secondary liver and/or kidney failure.PrognosisPrognosis is poor and most patients die at a young age from multiple-organ failure with predominant liver and renal dysfunction.Visit the Orphanet disease page for more resources.

MalaCards based summary : Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus, also known as wolcott-rallison syndrome, is related to neonatal diabetes mellitus and diabetes mellitus, permanent neonatal. An important gene associated with Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus is EIF2AK3 (Eukaryotic Translation Initiation Factor 2 Alpha Kinase 3), and among its related pathways/superpathways are Protein processing in endoplasmic reticulum and Potassium Channels. Affiliated tissues include liver, pancreas and bone, and related phenotypes are osteopenia and short stature

Disease Ontology : 12 A characterized by autosomal recessive inheritance of permanent neonatal diabetes mellitus with multiple epiphyseal dysplasia, osteoporosis, growth retardation and frequently hepatic and renal dysfunction that has material basis in homozygous mutation in the EIF2AK3 gene on chromosome 2p11.2.

OMIM : 58 Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by permanent neonatal or early infancy insulin-dependent diabetes. Epiphyseal dysplasia, osteoporosis, and growth retardation develop at a later age. Other frequent multisystem manifestations include hepatic and renal dysfunction, mental retardation, and cardiovascular abnormalities (summary by Delepine et al., 2000). (226980)

UniProtKB/Swiss-Prot : 76 Wolcott-Rallison syndrome: A rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.

Wikipedia : 77 Wolcott–Rallison syndrome, WRS, is a rare, autosomal recessive disorder with infancy-onset diabetes... more...

Related Diseases for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 68)
# Related Disease Score Top Affiliating Genes
1 neonatal diabetes mellitus 30.2 ABCC8 EIF2AK3 KCNJ11
2 diabetes mellitus, permanent neonatal 30.1 ABCC8 EIF2AK3 KCNJ11
3 blood group--wright antigen 12.1
4 wiedemann-rautenstrauch syndrome 11.6
5 blood group, diego system 11.4
6 long qt syndrome 1 11.4
7 diabetes mellitus 10.7
8 malaria 10.6
9 hypothyroidism 10.6
10 vaccinia 10.5
11 spondyloepiphyseal dysplasia with congenital joint dislocations 10.3
12 renal dysplasia, cystic 10.3
13 infantile liver failure syndrome 1 10.3
14 acute liver failure 10.3
15 hepatitis 10.3
16 liver disease 10.3
17 double outlet right ventricle 10.3
18 hypoaldosteronism 10.3
19 multicystic dysplastic kidney 10.3
20 prostate cancer 10.1
21 prostate cancer, hereditary, 8 10.1
22 prostate cancer, hereditary, 6 10.1
23 degos 'en cocarde' erythrokeratoderma 10.1
24 bladder cancer 10.1
25 carpal tunnel syndrome 10.1
26 mononeuropathy of the median nerve, mild 10.1
27 blood group, junior system 10.1
28 spinal muscular atrophy 10.1
29 wrinkles 10.1
30 osteomyelitis 10.1
31 fibromyalgia 10.1
32 muscular atrophy 10.1
33 retinoblastoma 9.9
34 rheumatoid arthritis 9.9
35 suppressor of tumorigenicity 3 9.9
36 thymoma, familial 9.9
37 asthma 9.9
38 salla disease 9.9
39 cutaneous leishmaniasis 9.9
40 pemphigus foliaceus 9.9
41 inflammatory bowel disease 9.9
42 scoliosis 9.9
43 plasmodium vivax malaria 9.9
44 plasmodium falciparum malaria 9.9
45 thymoma 9.9
46 leishmaniasis 9.9
47 hypoxia 9.9
48 munchausen by proxy 9.8 ABCC8 KCNJ11
49 cardiomyopathy, dilated, 1o 9.8 ABCC8 KCNJ11
50 acute insulin response 9.8 ABCC8 KCNJ11

Graphical network of the top 20 diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:



Diseases related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus

Symptoms & Phenotypes for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Human phenotypes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

60 33 (show top 50) (show all 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteopenia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000938
2 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
3 renal tubular dysfunction 60 33 hallmark (90%) Very frequent (99-80%) HP:0000124
4 dehydration 60 33 hallmark (90%) Very frequent (99-80%) HP:0001944
5 osteoporosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000939
6 hyperuricemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002149
7 weight loss 60 33 hallmark (90%) Very frequent (99-80%) HP:0001824
8 abnormality of the metaphysis 60 33 hallmark (90%) Very frequent (99-80%) HP:0000944
9 epiphyseal dysplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002656
10 epicanthus 60 33 hallmark (90%) Very frequent (99-80%) HP:0000286
11 microdontia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000691
12 high forehead 60 33 hallmark (90%) Very frequent (99-80%) HP:0000348
13 thin vermilion border 60 33 hallmark (90%) Very frequent (99-80%) HP:0000233
14 triangular face 60 33 hallmark (90%) Very frequent (99-80%) HP:0000325
15 cone-shaped epiphyses of the phalanges of the hand 60 33 hallmark (90%) Very frequent (99-80%) HP:0010230
16 glycosuria 60 33 hallmark (90%) Very frequent (99-80%) HP:0003076
17 steatorrhea 60 33 hallmark (90%) Very frequent (99-80%) HP:0002570
18 hyperglycemia 60 33 hallmark (90%) Very frequent (99-80%) HP:0003074
19 hypermetropia 60 33 hallmark (90%) Very frequent (99-80%) HP:0000540
20 multiple epiphyseal dysplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002654
21 transient neonatal diabetes mellitus 60 33 hallmark (90%) Very frequent (99-80%) HP:0008255
22 genu valgum 60 33 frequent (33%) Frequent (79-30%) HP:0002857
23 intellectual disability 60 33 frequent (33%) Frequent (79-30%) HP:0001249
24 muscular hypotonia 60 33 frequent (33%) Frequent (79-30%) HP:0001252
25 gait disturbance 60 33 frequent (33%) Frequent (79-30%) HP:0001288
26 hepatomegaly 60 33 frequent (33%) Frequent (79-30%) HP:0002240
27 delayed skeletal maturation 60 33 frequent (33%) Frequent (79-30%) HP:0002750
28 platyspondyly 60 33 frequent (33%) Frequent (79-30%) HP:0000926
29 coxa valga 60 33 frequent (33%) Frequent (79-30%) HP:0002673
30 short thorax 60 33 frequent (33%) Frequent (79-30%) HP:0010306
31 enlarged thorax 60 33 frequent (33%) Frequent (79-30%) HP:0100625
32 elevated hepatic transaminase 60 33 frequent (33%) Frequent (79-30%) HP:0002910
33 motor delay 60 33 frequent (33%) Frequent (79-30%) HP:0001270
34 hip dislocation 60 33 frequent (33%) Frequent (79-30%) HP:0002827
35 brachydactyly 60 33 frequent (33%) Frequent (79-30%) HP:0001156
36 neutropenia 60 33 frequent (33%) Frequent (79-30%) HP:0001875
37 acute hepatic failure 60 33 frequent (33%) Frequent (79-30%) HP:0006554
38 narrow iliac wings 60 33 frequent (33%) Frequent (79-30%) HP:0002868
39 chronic hepatic failure 60 33 frequent (33%) Frequent (79-30%) HP:0100626
40 abnormal heart morphology 60 33 frequent (33%) Frequent (79-30%) HP:0001627
41 ketoacidosis 60 33 frequent (33%) Frequent (79-30%) HP:0001993
42 intracerebral periventricular calcifications 60 33 frequent (33%) Frequent (79-30%) HP:0007229
43 hypothyroidism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000821
44 seizures 60 33 occasional (7.5%) Occasional (29-5%) HP:0001250
45 kyphosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002808
46 hyperlordosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0003307
47 microcephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000252
48 renal insufficiency 60 33 occasional (7.5%) Occasional (29-5%) HP:0000083
49 nephropathy 60 33 occasional (7.5%) Occasional (29-5%) HP:0000112
50 hypoglycemia 60 33 occasional (7.5%) Occasional (29-5%) HP:0001943

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
hypertelorism
upslanting palpebral fissures

Abdomen Liver:
hepatomegaly

Head And Neck Head:
microcephaly

Neurologic Central Nervous System:
hypertonia
developmental delay

Skeletal:
osteoporosis
multiple epiphyseal dysplasia

Skeletal Pelvis:
coxa valga
hip dislocation
narrow iliac wings
hip subluxation
reabsorption of capital femoral epiphyses

Abdomen Pancreas:
reduced pancreatic beta cells

Head And Neck Ears:
preauricular pits

Skeletal Feet:
ivory epiphyses
small, irregular tarsal centers
hypoplastic middle and distal phalanges

Skeletal Limbs:
genu valgum
bowing distal radii and ulnae
small, flattened epiphyses

Head And Neck Nose:
depressed nasal bridge

Growth Height:
short stature

Genitourinary Kidneys:
renal insufficiency

Skeletal Spine:
platyspondyly
lordosis
odontoid hypoplasia
irregular endplates

Chest External Features:
barrel-shaped chest

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
small, irregular carpal centers
cone-shaped epiphyses (proximal phalanges)
ivory epiphyses
disproportionately short middle phalanges

Endocrine Features:
insulin-dependent diabetes mellitus (onset in infancy)

Clinical features from OMIM:

226980

GenomeRNAi Phenotypes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

27 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-142 9.4 PPP1R15B
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-150 9.4 KCNJ11
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-171 9.4 KCNJ11
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-179 9.4 KCNJ11
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-187 9.4 KCNJ11
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-216 9.4 PPP1R15B
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-28 9.4 PPP1R15B
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-53 9.4 PPP1R15B
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-55 9.4 PPP1R15B
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-71 9.4 KCNJ11 PPP1R15B
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-84 9.4 PPP1R15B

Drugs & Therapeutics for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Search Clinical Trials , NIH Clinical Center for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus

Cochrane evidence based reviews: wolcott-rallison syndrome

Genetic Tests for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Anatomical Context for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

MalaCards organs/tissues related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

42
Liver, Pancreas, Bone, Kidney, Testes, Heart, Prostate

Publications for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Articles related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

(show top 50) (show all 52)
# Title Authors Year
1
Wolcott-Rallison syndrome due to the same mutation in EIF2AK3 (c.205G>T) in two unrelated families: A case report. ( 30906465 )
2019
2
Wolcott-Rallison Syndrome With Different Clinical Presentations and Genetic Patterns in Two Infants: Erratum. ( 31008890 )
2019
3
An Infant With Neonatal Diabetes and Double Outlet Right Ventricle - Wolcott- Rallison syndrome. ( 30514997 )
2018
4
Novel splice site mutation in EIF2AK3 gene causes Wolcott-Rallison syndrome in a consanguineous family from Saudi Arabia. ( 28220546 )
2018
5
A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes. ( 28843469 )
2018
6
Wolcott-Rallison Syndrome With Different Clinical Presentations and Genetic Patterns in 2 Infants. ( 30234637 )
2018
7
Multicystic dysplastic kidney: a new association of Wolcott-Rallison syndrome. ( 28955442 )
2017
8
Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome. ( 28652565 )
2017
9
Relative hypoaldosteronism in a patient with Wolcott-Rallison syndrome. ( 26433138 )
2016
10
En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with Wolcott-Rallison syndrome. ( 26784269 )
2016
11
Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. ( 26860746 )
2016
12
Wolcott-Rallison Syndrome with Novel EIF2AK3 Gene Mutation. ( 27145240 )
2016
13
THE 3rd W522X MUTATION IN EIF2AK3 GENE FROM TURKEY: A NEW PATIENT WITH WOLCOTT-RALLISON SYNDROME. ( 30204972 )
2016
14
Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. ( 25131821 )
2015
15
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. ( 25101713 )
2015
16
Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome. ( 25384546 )
2015
17
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. ( 25659842 )
2015
18
Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings. ( 25960841 )
2015
19
Primary hypothyroidism: an unusual manifestation of Wolcott-Rallison syndrome. ( 23933668 )
2014
20
Primary hypothyroidism and nipple hypoplasia in a girl with Wolcott-Rallison syndrome. ( 24194294 )
2014
21
EIF2AK3 mutations in South Indian children with permanent neonatal diabetes mellitus associated with Wolcott-Rallison syndrome. ( 24168455 )
2014
22
Wolcott Rallison syndrome: a rare inherited diabetes mellitus. ( 24710710 )
2014
23
Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome. ( 24859506 )
2014
24
Variable phenotype in five patients with Wolcott-Rallison syndrome due to the same EIF2AK3 (c.1259delA) mutation. ( 23585173 )
2013
25
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. ( 23759358 )
2013
26
Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3 Leading to Wolcott-Rallison Syndrome. ( 24032041 )
2013
27
Frequency and spectrum of Wolcott-Rallison syndrome in Saudi Arabia: a systematic review. ( 28156240 )
2013
28
Wolcott-Rallison syndrome due to a novel mutation (R491X) in EIF2AK3 gene. ( 22672868 )
2012
29
Wolcott-Rallison syndrome. ( 23263430 )
2012
30
Two novel mutations in the EIF2AK3 gene in children with Wolcott-Rallison syndrome. ( 21518408 )
2011
31
A novel EIF2AK3 mutation leading to Wolcott-Rallison syndrome in a Chinese child. ( 21648287 )
2011
32
Wolcott-Rallison syndrome due to the same mutation (W522X) in EIF2AK3 in two unrelated families and review of the literature. ( 20202148 )
2010
33
Wolcott-Rallison syndrome. ( 21050479 )
2010
34
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. ( 19837917 )
2009
35
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. ( 18704764 )
2008
36
Wolcott-Rallison syndrome with 3-hydroxydicarboxylic aciduria and lethal outcome. ( 18500571 )
2008
37
A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome. ( 16813601 )
2006
38
Re: EIF2AK3 mutations in patients with Wolcott-Rallison syndrome. ( 16212134 )
2005
39
Wolcott-Rallison Syndrome: clinical, genetic, and functional study of EIF2AK3 mutations and suggestion of genetic heterogeneity. ( 15220213 )
2004
40
Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. ( 15384883 )
2004
41
Wolcott-Rallison syndrome in a Bedouin boy. ( 15646169 )
2004
42
Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3. ( 12960215 )
2003
43
Loss of kinase activity in a patient with Wolcott-Rallison syndrome caused by a novel mutation in the EIF2AK3 gene. ( 12086964 )
2002
44
Wolcott-Rallison syndrome in two siblings with isolated central hypothyroidism. ( 12210348 )
2002
45
Wolcott-Rallison syndrome: clinical, radiological and histological findings in a Saudi child. ( 17264596 )
2001
46
EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. ( 10932183 )
2000
47
Wolcott-Rallison syndrome: a case with endocrine and exocrine pancreatic deficiency and pancreatic hypotrophy. ( 10968248 )
2000
48
Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome. ( 9598721 )
1998
49
Autopsy findings in the Wolcott-Rallison syndrome. ( 9185226 )
1997
50
Wolcott-Rallison syndrome associated with congenital malformations and a mosaic deletion 15q 11-12. ( 8737981 )
1996

Variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

UniProtKB/Swiss-Prot genetic disease variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

76
# Symbol AA change Variation ID SNP ID
1 EIF2AK3 p.Arg588Gln VAR_011408 rs121908569

ClinVar genetic disease variations for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

6 (show top 50) (show all 116)
# Gene Variation Type Significance SNP ID Assembly Location
1 EIF2AK3 NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs) duplication Pathogenic rs869025178 GRCh37 Chromosome 2, 88890091: 88890091
2 EIF2AK3 NM_004836.6(EIF2AK3): c.1035dupT (p.Lys346Terfs) duplication Pathogenic rs869025178 GRCh38 Chromosome 2, 88590573: 88590573
3 EIF2AK3 NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln) single nucleotide variant Pathogenic rs121908569 GRCh37 Chromosome 2, 88882948: 88882948
4 EIF2AK3 NM_004836.6(EIF2AK3): c.1763G> A (p.Arg588Gln) single nucleotide variant Pathogenic rs121908569 GRCh38 Chromosome 2, 88583430: 88583430
5 EIF2AK3 NM_004836.6(EIF2AK3): c.2985+1G> A single nucleotide variant Pathogenic rs869025179 GRCh37 Chromosome 2, 88870391: 88870391
6 EIF2AK3 NM_004836.6(EIF2AK3): c.2985+1G> A single nucleotide variant Pathogenic rs869025179 GRCh38 Chromosome 2, 88570873: 88570873
7 EIF2AK3 NM_004836.6(EIF2AK3): c.1570_1573del (p.Glu524Terfs) deletion Pathogenic GRCh37 Chromosome 2, 88885436: 88885439
8 EIF2AK3 NM_004836.6(EIF2AK3): c.1570_1573del (p.Glu524Terfs) deletion Pathogenic GRCh38 Chromosome 2, 88585918: 88585921
9 EIF2AK3 NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter) single nucleotide variant Pathogenic rs121908570 GRCh37 Chromosome 2, 88890344: 88890344
10 EIF2AK3 NM_004836.6(EIF2AK3): c.994G> T (p.Glu332Ter) single nucleotide variant Pathogenic rs121908570 GRCh38 Chromosome 2, 88590826: 88590826
11 EIF2AK3 NM_004836.6(EIF2AK3): c.1756A> T (p.Ile586Leu) single nucleotide variant Benign/Likely benign rs75385605 GRCh37 Chromosome 2, 88882955: 88882955
12 EIF2AK3 NM_004836.6(EIF2AK3): c.1756A> T (p.Ile586Leu) single nucleotide variant Benign/Likely benign rs75385605 GRCh38 Chromosome 2, 88583437: 88583437
13 EIF2AK3 NM_004836.6(EIF2AK3): c.1763+6A> T single nucleotide variant Benign rs6750998 GRCh37 Chromosome 2, 88882942: 88882942
14 EIF2AK3 NM_004836.6(EIF2AK3): c.1763+6A> T single nucleotide variant Benign rs6750998 GRCh38 Chromosome 2, 88583424: 88583424
15 EIF2AK3 NM_004836.6(EIF2AK3): c.1791A> G (p.Gln597=) single nucleotide variant Benign rs1805164 GRCh37 Chromosome 2, 88879131: 88879131
16 EIF2AK3 NM_004836.6(EIF2AK3): c.1791A> G (p.Gln597=) single nucleotide variant Benign rs1805164 GRCh38 Chromosome 2, 88579613: 88579613
17 EIF2AK3 NM_004836.6(EIF2AK3): c.2110G> T (p.Ala704Ser) single nucleotide variant Benign rs1805165 GRCh37 Chromosome 2, 88874891: 88874891
18 EIF2AK3 NM_004836.6(EIF2AK3): c.2110G> T (p.Ala704Ser) single nucleotide variant Benign rs1805165 GRCh38 Chromosome 2, 88575373: 88575373
19 EIF2AK3 NM_004836.6(EIF2AK3): c.407C> G (p.Ser136Cys) single nucleotide variant Benign rs867529 GRCh37 Chromosome 2, 88913273: 88913273
20 EIF2AK3 NM_004836.6(EIF2AK3): c.407C> G (p.Ser136Cys) single nucleotide variant Benign rs867529 GRCh38 Chromosome 2, 88613755: 88613755
21 EIF2AK3 NM_004836.6(EIF2AK3): c.497A> G (p.Gln166Arg) single nucleotide variant Benign rs13045 GRCh37 Chromosome 2, 88895123: 88895123
22 EIF2AK3 NM_004836.6(EIF2AK3): c.497A> G (p.Gln166Arg) single nucleotide variant Benign rs13045 GRCh38 Chromosome 2, 88595605: 88595605
23 EIF2AK3 NM_004836.6(EIF2AK3): c.61_63del (p.Leu21del) deletion Benign rs1805190 GRCh37 Chromosome 2, 88926730: 88926732
24 EIF2AK3 NM_004836.6(EIF2AK3): c.61_63del (p.Leu21del) deletion Benign rs1805190 GRCh38 Chromosome 2, 88627212: 88627214
25 EIF2AK3 NM_004836.6(EIF2AK3): c.154G> A (p.Ala52Thr) single nucleotide variant Benign/Likely benign rs201593811 GRCh37 Chromosome 2, 88926639: 88926639
26 EIF2AK3 NM_004836.6(EIF2AK3): c.154G> A (p.Ala52Thr) single nucleotide variant Benign/Likely benign rs201593811 GRCh38 Chromosome 2, 88627121: 88627121
27 EIF2AK3 NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter) single nucleotide variant Pathogenic rs864621972 GRCh37 Chromosome 2, 88888393: 88888393
28 EIF2AK3 NM_004836.6(EIF2AK3): c.1192C> T (p.Gln398Ter) single nucleotide variant Pathogenic rs864621972 GRCh38 Chromosome 2, 88588875: 88588875
29 EIF2AK3 NM_004836.6(EIF2AK3): c.1564_1565del (p.Trp522Glufs) deletion Pathogenic rs797045558 GRCh37 Chromosome 2, 88885444: 88885445
30 EIF2AK3 NM_004836.6(EIF2AK3): c.1564_1565del (p.Trp522Glufs) deletion Pathogenic rs797045558 GRCh38 Chromosome 2, 88585926: 88585927
31 EIF2AK3 NM_004836.6(EIF2AK3): c.*870_*875del deletion Uncertain significance rs565147927 GRCh38 Chromosome 2, 88556861: 88556866
32 EIF2AK3 NM_004836.6(EIF2AK3): c.*870_*875del deletion Uncertain significance rs565147927 GRCh37 Chromosome 2, 88856379: 88856384
33 EIF2AK3 NM_004836.6(EIF2AK3): c.*360C> T single nucleotide variant Uncertain significance rs551581209 GRCh38 Chromosome 2, 88557376: 88557376
34 EIF2AK3 NM_004836.6(EIF2AK3): c.*360C> T single nucleotide variant Uncertain significance rs551581209 GRCh37 Chromosome 2, 88856894: 88856894
35 EIF2AK3 NM_004836.6(EIF2AK3): c.*310_*311dup duplication Uncertain significance rs767645334 GRCh38 Chromosome 2, 88557425: 88557426
36 EIF2AK3 NM_004836.6(EIF2AK3): c.*310_*311dup duplication Uncertain significance rs767645334 GRCh37 Chromosome 2, 88856943: 88856944
37 EIF2AK3 NM_004836.6(EIF2AK3): c.2532T> C (p.Ser844=) single nucleotide variant Uncertain significance rs56094918 GRCh38 Chromosome 2, 88574951: 88574951
38 EIF2AK3 NM_004836.6(EIF2AK3): c.2532T> C (p.Ser844=) single nucleotide variant Uncertain significance rs56094918 GRCh37 Chromosome 2, 88874469: 88874469
39 EIF2AK3 NM_004836.6(EIF2AK3): c.2500G> A (p.Ala834Thr) single nucleotide variant Uncertain significance rs751296708 GRCh38 Chromosome 2, 88574983: 88574983
40 EIF2AK3 NM_004836.6(EIF2AK3): c.2500G> A (p.Ala834Thr) single nucleotide variant Uncertain significance rs751296708 GRCh37 Chromosome 2, 88874501: 88874501
41 EIF2AK3 NM_004836.6(EIF2AK3): c.2237T> C (p.Met746Thr) single nucleotide variant Uncertain significance rs201662849 GRCh38 Chromosome 2, 88575246: 88575246
42 EIF2AK3 NM_004836.6(EIF2AK3): c.2237T> C (p.Met746Thr) single nucleotide variant Uncertain significance rs201662849 GRCh37 Chromosome 2, 88874764: 88874764
43 EIF2AK3 NM_004836.6(EIF2AK3): c.2093G> A (p.Arg698His) single nucleotide variant Uncertain significance rs780592115 GRCh38 Chromosome 2, 88575390: 88575390
44 EIF2AK3 NM_004836.6(EIF2AK3): c.2093G> A (p.Arg698His) single nucleotide variant Uncertain significance rs780592115 GRCh37 Chromosome 2, 88874908: 88874908
45 EIF2AK3 NM_004836.6(EIF2AK3): c.1165+10T> C single nucleotide variant Uncertain significance rs745614562 GRCh38 Chromosome 2, 88590433: 88590433
46 EIF2AK3 NM_004836.6(EIF2AK3): c.1165+10T> C single nucleotide variant Uncertain significance rs745614562 GRCh37 Chromosome 2, 88889951: 88889951
47 EIF2AK3 NM_004836.6(EIF2AK3): c.-195G> T single nucleotide variant Uncertain significance rs886056421 GRCh38 Chromosome 2, 88627469: 88627469
48 EIF2AK3 NM_004836.6(EIF2AK3): c.-195G> T single nucleotide variant Uncertain significance rs886056421 GRCh37 Chromosome 2, 88926987: 88926987
49 EIF2AK3 NM_004836.6(EIF2AK3): c.*459G> T single nucleotide variant Uncertain significance rs886056412 GRCh38 Chromosome 2, 88557277: 88557277
50 EIF2AK3 NM_004836.6(EIF2AK3): c.*459G> T single nucleotide variant Uncertain significance rs886056412 GRCh37 Chromosome 2, 88856795: 88856795

Expression for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Search GEO for disease gene expression data for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus.

Pathways for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Pathways related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to KEGG:

38
# Name Kegg Source Accession
1 Protein processing in endoplasmic reticulum hsa04141

GO Terms for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

Cellular components related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sarcolemma GO:0042383 8.96 ABCC8 KCNJ11
2 inward rectifying potassium channel GO:0008282 8.62 ABCC8 KCNJ11

Biological processes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 potassium ion transport GO:0006813 9.4 ABCC8 KCNJ11
2 regulation of translation GO:0006417 9.37 EIF2AK3 PPP1R15B
3 potassium ion transmembrane transport GO:0071805 9.32 ABCC8 KCNJ11
4 response to endoplasmic reticulum stress GO:0034976 9.26 EIF2AK3 PPP1R15B
5 regulation of insulin secretion GO:0050796 9.16 ABCC8 KCNJ11
6 negative regulation of insulin secretion GO:0046676 8.96 ABCC8 KCNJ11
7 ER overload response GO:0006983 8.62 EIF2AK3 PPP1R15B

Molecular functions related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ATP binding GO:0005524 9.26 ABCC8 ALPK3 EIF2AK3 KCNJ11
2 ion channel binding GO:0044325 9.16 ABCC8 KCNJ11
3 ATP-activated inward rectifier potassium channel activity GO:0015272 8.32 KCNJ11

Sources for Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes...

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