WRS
MCID: EPP024
MIFTS: 55

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 56
Wolcott-Rallison Syndrome 56 12 74 58 73 36 13 54 43 15 39 71
Med-Iddm Syndrome 56 52 73
Iddm-Med Syndrome 56 52 73
Wrs 58 73
Epiphyseal Dysplasia Multiple with Early-Onset Diabetes Mellitus 52
Early-Onset Diabetes Mellitus with Multiple Epiphyseal Dysplasia 58
Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus 73
Wolcott Rallison Syndrome 52

Characteristics:

Orphanet epidemiological data:

58
wolcott-rallison syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
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:

31
epiphyseal dysplasia, multiple, with early-onset diabetes mellitus:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare bone diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


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

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1667 Definition Wolcott-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. Epidemiology Fewer 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 description Diabetes 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. Etiology WRS 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 methods Diagnosis 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 diagnosis Differential 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 diagnosis Antenatal diagnosis should be offered to parents of a WRS patient with confirmed EIF2AK3 mutation. Genetic counseling Inheritance is autosomal recessive and genetic counseling is possible. Management and treatment Close 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. Prognosis Prognosis 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 diabetes mellitus, ketosis-prone and diabetes mellitus. 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 Metabolism of proteins. Affiliated tissues include liver, bone and kidney, and related phenotypes are osteopenia and short stature

Disease Ontology : 12 An autosomal recessive disease that is characterized by 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 eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) gene on chromosome 2p11.2.

OMIM : 56 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)

KEGG : 36 Wolcott-Rallison syndrome is a rare autosomal recessive disorder characterized by neonatal insulin-requiring diabetes and associated with skeletal dysplasia and growth retardation. Diabetes appears during the first months of life in most patients and major skeletal manifestations include the long bones, pelvis and vertebrae. Liver is also affected in the disease.

UniProtKB/Swiss-Prot : 73 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 : 74 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 141)
# Related Disease Score Top Affiliating Genes
1 diabetes mellitus, ketosis-prone 30.5 KCNJ11 INS ABCC8
2 diabetes mellitus 29.0 WFS1 PTF1A KCNJ11 INS GLIS3 DNAJC3
3 neonatal diabetes mellitus 28.0 WFS1 RFX6 PTF1A KCNJ11 INS IER3IP1
4 diabetes mellitus, permanent neonatal 28.0 WFS1 RFX6 PTF1A KCNJ11 INS IER3IP1
5 blood group--wright antigen 11.9
6 wiedemann-rautenstrauch syndrome 11.8
7 blood group, diego system 11.5
8 long qt syndrome 1 11.5
9 autosomal recessive disease 11.0
10 hypothyroidism 10.9
11 multiple epiphyseal dysplasia 10.9
12 neutropenia 10.8
13 acute liver failure 10.7
14 spondyloepiphyseal dysplasia with congenital joint dislocations 10.6
15 microcephaly 10.6
16 vaccinia 10.5
17 hypoglycemia 10.5
18 specific language disorder 10.5
19 diabetes mellitus, insulin-dependent 10.4
20 endocardial fibroelastosis 10.4
21 hepatitis a 10.4
22 acute kidney tubular necrosis 10.4
23 exocrine pancreatic insufficiency 10.4
24 autoimmune hepatitis 10.4
25 euthyroid sick syndrome 10.4
26 acute kidney failure 10.4
27 myopathy 10.4
28 kidney disease 10.4
29 double outlet right ventricle 10.4
30 mitochondrial disorders 10.4
31 hypoadrenalism 10.4
32 hypoaldosteronism 10.4
33 pachygyria 10.4
34 posttransplant acute limbic encephalitis 10.4
35 multicystic dysplastic kidney 10.4
36 inflammatory myopathy with abundant macrophages 10.4
37 munchausen by proxy 10.3 KCNJ11 ABCC8
38 maturity-onset diabetes of the young, type 11 10.3 KCNJ11 ABCC8
39 maturity-onset diabetes of the young, type 13 10.3 KCNJ11 ABCC8
40 maturity-onset diabetes of the young, type 8, with exocrine dysfunction 10.3 KCNJ11 ABCC8
41 maturity-onset diabetes of the young, type 7 10.3 KCNJ11 ABCC8
42 malaria 10.3
43 maturity-onset diabetes of the young, type 9 10.3 KCNJ11 ABCC8
44 ileocolitis 10.3 XBP1 DNAJC3
45 maturity-onset diabetes of the young, type 6 10.2 KCNJ11 ABCC8
46 cantu syndrome 10.2 KCNJ11 ABCC8
47 hypertriglyceridemia, familial 10.2
48 diarrhea 10.2
49 muscular atrophy 10.2
50 cardiomyopathy, dilated, 1o 10.2 KCNJ11 ABCC8

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:

58 31 (show top 50) (show all 83)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 osteopenia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000938
2 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
3 renal tubular dysfunction 58 31 hallmark (90%) Very frequent (99-80%) HP:0000124
4 dehydration 58 31 hallmark (90%) Very frequent (99-80%) HP:0001944
5 osteoporosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000939
6 hyperuricemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002149
7 weight loss 58 31 hallmark (90%) Very frequent (99-80%) HP:0001824
8 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000944
9 epiphyseal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002656
10 epicanthus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000286
11 microdontia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000691
12 thin vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0000233
13 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
14 triangular face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000325
15 cone-shaped epiphyses of the phalanges of the hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0010230
16 glycosuria 58 31 hallmark (90%) Very frequent (99-80%) HP:0003076
17 hyperglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003074
18 steatorrhea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002570
19 hypermetropia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000540
20 multiple epiphyseal dysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002654
21 transient neonatal diabetes mellitus 58 31 hallmark (90%) Very frequent (99-80%) HP:0008255
22 genu valgum 58 31 frequent (33%) Frequent (79-30%) HP:0002857
23 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
24 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
25 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
26 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
27 delayed skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0002750
28 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
29 platyspondyly 58 31 frequent (33%) Frequent (79-30%) HP:0000926
30 coxa valga 58 31 frequent (33%) Frequent (79-30%) HP:0002673
31 short thorax 58 31 frequent (33%) Frequent (79-30%) HP:0010306
32 enlarged thorax 58 31 frequent (33%) Frequent (79-30%) HP:0100625
33 elevated hepatic transaminase 58 31 frequent (33%) Frequent (79-30%) HP:0002910
34 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
35 hip dislocation 58 31 frequent (33%) Frequent (79-30%) HP:0002827
36 neutropenia 58 31 frequent (33%) Frequent (79-30%) HP:0001875
37 abnormal heart morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001627
38 acute hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0006554
39 narrow iliac wings 58 31 frequent (33%) Frequent (79-30%) HP:0002868
40 intracerebral periventricular calcifications 58 31 frequent (33%) Frequent (79-30%) HP:0007229
41 chronic hepatic failure 58 31 frequent (33%) Frequent (79-30%) HP:0100626
42 ketoacidosis 58 31 frequent (33%) Frequent (79-30%) HP:0001993
43 seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0001250
44 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
45 hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000821
46 hyperlordosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003307
47 intrauterine growth retardation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001511
48 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
49 nephropathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000112
50 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
upslanting palpebral fissures

Abdomen Liver:
hepatomegaly

Growth Height:
short stature

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

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

Head And Neck Ears:
preauricular pits

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

Head And Neck Nose:
depressed nasal bridge

Head And Neck Head:
microcephaly

Genitourinary Kidneys:
renal insufficiency

Skeletal Spine:
platyspondyly
lordosis
odontoid hypoplasia
irregular endplates

Chest External Features:
barrel-shaped chest

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

Head And Neck Mouth:
high-arched palate

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

Clinical features from OMIM:

226980

MGI Mouse Phenotypes related to Epiphyseal Dysplasia, Multiple, with Early-Onset Diabetes Mellitus:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.2 ATF4 ATF6 DNAJC3 EIF2AK3 EIF2AK4 EIF2S1
2 endocrine/exocrine gland MP:0005379 10.18 ABCC8 ATF4 ATF6 DNAJC3 EIF2AK3 EIF2S1
3 behavior/neurological MP:0005386 10.17 DNAJC3 EIF2AK3 EIF2AK4 EIF2S1 INS KCNJ11
4 homeostasis/metabolism MP:0005376 10.13 ABCC8 ATF4 ATF6 DNAJC3 EIF2AK3 EIF2AK4
5 digestive/alimentary MP:0005381 10.01 ATF4 DNAJC3 EIF2AK3 INS PTF1A RFX6
6 mortality/aging MP:0010768 9.83 ATF4 ATF6 DNAJC3 EIF2AK3 EIF2AK4 EIF2S1
7 liver/biliary system MP:0005370 9.76 ATF4 ATF6 EIF2AK3 EIF2AK4 INS PPP1R15B
8 no phenotypic analysis MP:0003012 9.17 ABCC8 ATF6 EIF2AK3 GLIS3 INS KCNJ11

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:

40
Liver, Bone, Kidney, Pancreas, Testes, Heart, Brain

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 94)
# Title Authors PMID Year
1
A novel mutation in the EIF2AK3 gene with variable expressivity in two patients with Wolcott-Rallison syndrome. 54 61 56 6
16813601 2006
2
EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. 54 61 56 6
10932183 2000
3
Wolcott-Rallison syndrome: pathogenic insights into neonatal diabetes from new mutation and expression studies of EIF2AK3. 61 56 6
12960215 2003
4
Wolcott-Rallison syndrome. 61 56 6
7551159 1995
5
Wolcott-Rallison syndrome in two siblings with isolated central hypothyroidism. 61 56
12210348 2002
6
Wolcott-Rallison syndrome: clinical, radiological and histological findings in a Saudi child. 61 56
17264596 2001
7
Organisation of the human PAX4 gene and its exclusion as a candidate for the Wolcott-Rallison syndrome. 61 56
9598721 1998
8
Wolcott-Rallison syndrome associated with congenital malformations and a mosaic deletion 15q 11-12. 61 56
8737981 1996
9
Wolcott-Rallison syndrome: diabetes mellitus and spondyloepiphyseal dysplasia. 61 56
7094931 1982
10
Infancy-onset diabetes mellitus and multiple epiphyseal dysplasia. 56
5008828 1972
11
Recurrent acute liver failure and mitochondriopathy in a case of Wolcott-Rallison syndrome. 54 61
18704764 2008
12
PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasis. 54 61
17141632 2006
13
Microcephaly and simplified gyral pattern of the brain associated with early onset insulin-dependent diabetes mellitus. 54 61
16972080 2006
14
The EIF2AK3 gene region and type I diabetes in subjects from South India. 54 61
15483661 2004
15
Wolcott-Rallison syndrome: a clinical and genetic study of three children, novel mutation in EIF2AK3 and a review of the literature. 54 61
15384883 2004
16
Phenotypic and genetic analyses of subcongenic BB.SHR rat lines shorten the region on chromosome 4 bearing gene(s) for underlying facets of metabolic syndrome. 54 61
15173549 2004
17
Endoplasmic reticulum stress and the development of diabetes: a review. 54 61
12475790 2002
18
Wolcott-Rallison Syndrome- Endocrinopathy with Recurrent Acute Liver Failure. 61
31884440 2019
19
First European Case of Simultaneous Liver and Pancreas Transplantation as Treatment of Wolcott-Rallison Syndrome in a Small Child. 61
31335762 2019
20
Practical management in Wolcott-Rallison syndrome with associated hypothyroidism, neutropenia, and recurrent liver failure: A case report. 61
31183082 2019
21
Wolcott-Rallison syndrome in Iran: a common cause of neonatal diabetes. 61
31141482 2019
22
Wolcott-Rallison Syndrome With Different Clinical Presentations and Genetic Patterns in Two Infants: Erratum. 61
31008890 2019
23
Wolcott-Rallison syndrome due to the same mutation in EIF2AK3 (c.205G>T) in two unrelated families: A case report. 61
30906465 2019
24
EIF2AK3 novel mutation in a child with early-onset diabetes mellitus, a case report. 61
30922274 2019
25
[A case report of EIF2AK3-related Wolcott-Rallison syndrome and literature review]. 61
30782283 2019
26
Tauopathy-associated PERK alleles are functional hypomorphs that increase neuronal vulnerability to ER stress. 61
30137327 2018
27
An Infant With Neonatal Diabetes and Double Outlet Right Ventricle - Wolcott- Rallison syndrome. 61
30514997 2018
28
Wolcott-Rallison Syndrome With Different Clinical Presentations and Genetic Patterns in 2 Infants. 61
30234637 2018
29
A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes. 61
28843469 2018
30
Novel splice site mutation in EIF2AK3 gene causes Wolcott-Rallison syndrome in a consanguineous family from Saudi Arabia. 61
28220546 2018
31
Ketoacidosis in Neonatal Diabetes Mellitus, Part of Wolcott-Rallison Syndrome. 61
28652565 2017
32
Multicystic dysplastic kidney: a new association of Wolcott-Rallison syndrome. 61
28955442 2017
33
Wolcott-Rallison Syndrome with Novel EIF2AK3 Gene Mutation. 61
27145240 2016
34
Relative hypoaldosteronism in a patient with Wolcott-Rallison syndrome. 61
26433138 2016
35
En bloc multiorgan transplant (liver, pancreas, and kidney) for acute liver and renal failure in a patient with Wolcott-Rallison syndrome. 61
26784269 2016
36
Infantile onset diabetes mellitus in developing countries - India. 61
27022444 2016
37
Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates. 61
26463504 2016
38
Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. 61
26860746 2016
39
THE 3rd W522X MUTATION IN EIF2AK3 GENE FROM TURKEY: A NEW PATIENT WITH WOLCOTT-RALLISON SYNDROME. 61
30204972 2016
40
Type I interferons mediate pancreatic toxicities of PERK inhibition. 61
26627716 2015
41
Microscopic and ultrastructural features in Wolcott-Rallison syndrome, a permanent neonatal diabetes mellitus: about two autopsy cases. 61
25131821 2015
42
A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly. 61
26159176 2015
43
The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. 61
26231457 2015
44
Early Neurodegeneration in the Brain of a Child Without Functional PKR-like Endoplasmic Reticulum Kinase. 61
26172286 2015
45
Anaesthesia and orphan disease: a child with Wolcott-Rallison syndrome. 61
25101713 2015
46
Novel mutation in wolcott-rallison syndrome with variable expression in two omani siblings. 61
25960841 2015
47
Liver, pancreas and kidney transplantation for the treatment of Wolcott-Rallison syndrome. 61
25384546 2015
48
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. 61
25659842 2015
49
Primary hypothyroidism: an unusual manifestation of Wolcott-Rallison syndrome. 61
23933668 2014
50
Phenotypic heterogeneity in monogenic diabetes: the clinical and diagnostic utility of a gene panel-based next-generation sequencing approach. 61
25306193 2014

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

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

6 (show top 50) (show all 59) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 EIF2AK3 NM_004836.7(EIF2AK3):c.1192C>T (p.Gln398Ter)SNV Pathogenic 208168 rs864621972 2:88888393-88888393 2:88588875-88588875
2 EIF2AK3 NM_004836.7(EIF2AK3):c.1564_1565del (p.Trp522fs)deletion Pathogenic 210932 rs797045558 2:88885444-88885445 2:88585926-88585927
3 EIF2AK3 NM_004836.7(EIF2AK3):c.1035dup (p.Lys346Ter)duplication Pathogenic 5874 rs869025178 2:88890090-88890091 2:88590572-88590573
4 EIF2AK3 NM_004836.7(EIF2AK3):c.1763G>A (p.Arg588Gln)SNV Pathogenic 5875 rs121908569 2:88882948-88882948 2:88583430-88583430
5 EIF2AK3 NM_004836.7(EIF2AK3):c.2985+1G>ASNV Pathogenic 5876 rs869025179 2:88870391-88870391 2:88570873-88570873
6 EIF2AK3 NM_004836.7(EIF2AK3):c.1566_1569GAAA[1] (p.Lys523_Glu524insTer)short repeat Pathogenic 5877 rs1558652941 2:88885436-88885439 2:88585918-88585921
7 EIF2AK3 NM_004836.7(EIF2AK3):c.994G>T (p.Glu332Ter)SNV Pathogenic 5878 rs121908570 2:88890344-88890344 2:88590826-88590826
8 EIF2AK3 NM_004836.7(EIF2AK3):c.2758C>T (p.Gln920Ter)SNV Pathogenic 435051 rs1553407942 2:88874243-88874243 2:88574725-88574725
9 EIF2AK3 NM_004836.7(EIF2AK3):c.2707C>T (p.Arg903Ter)SNV Pathogenic 807600 2:88874294-88874294 2:88574776-88574776
10 EIF2AK3 NM_004836.7(EIF2AK3):c.3291A>G (p.Ser1097=)SNV Conflicting interpretations of pathogenicity 337399 rs10208681 2:88857314-88857314 2:88557796-88557796
11 EIF2AK3 NM_004836.7(EIF2AK3):c.2014G>A (p.Glu672Lys)SNV Conflicting interpretations of pathogenicity 337410 rs35226268 2:88876094-88876094 2:88576576-88576576
12 EIF2AK3 NM_004836.7(EIF2AK3):c.2532T>C (p.Ser844=)SNV Conflicting interpretations of pathogenicity 337401 rs56094918 2:88874469-88874469 2:88574951-88574951
13 EIF2AK3 NM_004836.7(EIF2AK3):c.1697A>T (p.Asp566Val)SNV Conflicting interpretations of pathogenicity 337412 rs55791823 2:88883014-88883014 2:88583496-88583496
14 EIF2AK3 NM_004836.7(EIF2AK3):c.1173T>C (p.Tyr391=)SNV Conflicting interpretations of pathogenicity 337416 rs146949180 2:88888412-88888412 2:88588894-88588894
15 EIF2AK3 NM_004836.7(EIF2AK3):c.1092T>A (p.Asn364Lys)SNV Uncertain significance 337418 rs886056417 2:88890034-88890034 2:88590516-88590516
16 EIF2AK3 NM_004836.7(EIF2AK3):c.68T>G (p.Leu23Arg)SNV Uncertain significance 337420 rs886056418 2:88926725-88926725 2:88627207-88627207
17 EIF2AK3 NM_004836.7(EIF2AK3):c.-162G>ASNV Uncertain significance 337423 rs886056420 2:88926954-88926954 2:88627436-88627436
18 EIF2AK3 NM_004836.7(EIF2AK3):c.*864_*869ATGTTT[1]short repeat Uncertain significance 337390 rs565147927 2:88856379-88856384 2:88556861-88556866
19 EIF2AK3 NM_004836.7(EIF2AK3):c.*360C>TSNV Uncertain significance 337394 rs551581209 2:88856894-88856894 2:88557376-88557376
20 EIF2AK3 NM_004836.7(EIF2AK3):c.*300_*301TA[7]short repeat Uncertain significance 337395 rs767645334 2:88856942-88856943 2:88557424-88557425
21 EIF2AK3 NM_004836.7(EIF2AK3):c.1307-4T>GSNV Uncertain significance 337415 rs548802949 2:88887626-88887626 2:88588108-88588108
22 EIF2AK3 NM_004836.7(EIF2AK3):c.719G>A (p.Arg240His)SNV Uncertain significance 337419 rs147458427 2:88892838-88892838 2:88593320-88593320
23 EIF2AK3 NM_004836.7(EIF2AK3):c.13A>G (p.Ile5Val)SNV Uncertain significance 337421 rs886056419 2:88926780-88926780 2:88627262-88627262
24 EIF2AK3 NM_004836.7(EIF2AK3):c.-17C>GSNV Uncertain significance 337422 rs755314163 2:88926809-88926809 2:88627291-88627291
25 EIF2AK3 NM_004836.6(EIF2AK3):c.-263T>CSNV Uncertain significance 337427 rs762232975 2:88927055-88927055 2:88627537-88627537
26 EIF2AK3 NM_004836.7(EIF2AK3):c.*635G>ASNV Uncertain significance 337391 rs180734302 2:88856619-88856619 2:88557101-88557101
27 EIF2AK3 NM_004836.7(EIF2AK3):c.*363_*364deldeletion Uncertain significance 337393 rs533135276 2:88856890-88856891 2:88557372-88557373
28 EIF2AK3 NM_004836.7(EIF2AK3):c.2507A>T (p.Lys836Ile)SNV Uncertain significance 337402 rs200270016 2:88874494-88874494 2:88574976-88574976
29 EIF2AK3 NM_004836.7(EIF2AK3):c.2073T>C (p.Asp691=)SNV Uncertain significance 337408 rs747687191 2:88874928-88874928 2:88575410-88575410
30 EIF2AK3 NM_004836.7(EIF2AK3):c.2064C>A (p.Ser688Arg)SNV Uncertain significance 337409 rs771612567 2:88874937-88874937 2:88575419-88575419
31 EIF2AK3 NM_004836.7(EIF2AK3):c.2500G>A (p.Ala834Thr)SNV Uncertain significance 337403 rs751296708 2:88874501-88874501 2:88574983-88574983
32 EIF2AK3 NM_004836.7(EIF2AK3):c.2237T>C (p.Met746Thr)SNV Uncertain significance 337404 rs201662849 2:88874764-88874764 2:88575246-88575246
33 EIF2AK3 NM_004836.7(EIF2AK3):c.2093G>A (p.Arg698His)SNV Uncertain significance 337406 rs780592115 2:88874908-88874908 2:88575390-88575390
34 EIF2AK3 NM_004836.7(EIF2AK3):c.1165+10T>CSNV Uncertain significance 337417 rs745614562 2:88889951-88889951 2:88590433-88590433
35 EIF2AK3 NM_004836.6(EIF2AK3):c.-195G>TSNV Uncertain significance 337425 rs886056421 2:88926987-88926987 2:88627469-88627469
36 EIF2AK3 NM_004836.7(EIF2AK3):c.*459G>TSNV Uncertain significance 337392 rs886056412 2:88856795-88856795 2:88557277-88557277
37 EIF2AK3 NM_004836.7(EIF2AK3):c.*271T>GSNV Uncertain significance 337397 rs886056414 2:88856983-88856983 2:88557465-88557465
38 EIF2AK3 NM_004836.7(EIF2AK3):c.*175A>TSNV Uncertain significance 337398 rs886056415 2:88857079-88857079 2:88557561-88557561
39 EIF2AK3 NM_004836.7(EIF2AK3):c.1601T>C (p.Ile534Thr)SNV Uncertain significance 337413 rs747376208 2:88885408-88885408 2:88585890-88585890
40 EIF2AK3 NM_004836.7(EIF2AK3):c.1332G>A (p.Leu444=)SNV Uncertain significance 337414 rs779731596 2:88887597-88887597 2:88588079-88588079
41 EIF2AK3 NM_004836.6(EIF2AK3):c.-201A>GSNV Uncertain significance 337426 rs144057685 2:88926993-88926993 2:88627475-88627475
42 EIF2AK3 NM_004836.7(EIF2AK3):c.*894_*897AATC[1]short repeat Uncertain significance 337389 rs886056411 2:88856353-88856356 2:88556835-88556838
43 EIF2AK3 NM_004836.7(EIF2AK3):c.*286G>CSNV Uncertain significance 337396 rs886056413 2:88856968-88856968 2:88557450-88557450
44 EIF2AK3 NM_004836.7(EIF2AK3):c.2736C>T (p.Ser912=)SNV Uncertain significance 337400 rs886056416 2:88874265-88874265 2:88574747-88574747
45 EIF2AK3 NM_004836.7(EIF2AK3):c.2135T>C (p.Ile712Thr)SNV Uncertain significance 337405 rs760433148 2:88874866-88874866 2:88575348-88575348
46 EIF2AK3 NM_004836.7(EIF2AK3):c.2092C>A (p.Arg698Ser)SNV Uncertain significance 337407 rs189064501 2:88874909-88874909 2:88575391-88575391
47 EIF2AK3 NM_004836.7(EIF2AK3):c.1719T>C (p.Asn573=)SNV Uncertain significance 337411 rs137927384 2:88882992-88882992 2:88583474-88583474
48 EIF2AK3 NM_004836.7(EIF2AK3):c.503G>A (p.Arg168His)SNV Uncertain significance 522521 rs1003629254 2:88895117-88895117 2:88595599-88595599
49 EIF2AK3 NM_004836.7(EIF2AK3):c.1751G>A (p.Gly584Glu)SNV Uncertain significance 393382 rs150314450 2:88882960-88882960 2:88583442-88583442
50 EIF2AK3 NM_004836.7(EIF2AK3):c.-172C>TSNV Likely benign 337424 rs71414432 2:88926964-88926964 2:88627446-88627446

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

73
# Symbol AA change Variation ID SNP ID
1 EIF2AK3 p.Arg588Gln VAR_011408 rs121908569

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:

36
# Name Kegg Source Accession
1 Protein processing in endoplasmic reticulum hsa04141

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

(show all 11)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.52 XBP1 WFS1 INS EIF2S1 EIF2AK3 DNAJC3
2 12.27 WFS1 INS ATF6 ATF4
3
Show member pathways
12.06 XBP1 WFS1 EIF2S1 EIF2AK3 DNAJC3 ATF6
4 12 XBP1 EIF2S1 EIF2AK4 EIF2AK3 DNAJC3
5 11.81 INS EIF2S1 EIF2AK4 EIF2AK3
6
Show member pathways
11.63 RFX6 PTF1A INS
7
Show member pathways
11.59 KCNJ11 INS ABCC8
8 11.5 XBP1 WFS1 PPP1R15A EIF2S1 EIF2AK4 EIF2AK3
9
Show member pathways
11.31 EIF2S1 EIF2AK3 ATF6 ATF4
10 11.22 KCNJ11 INS ABCC8
11 10.9 XBP1 PPP1R15A EIF2AK3 DNAJC3 ATF6 ATF4

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 endoplasmic reticulum membrane GO:0005789 9.8 XBP1 WFS1 PPP1R15A IER3IP1 EIF2AK3 ATF6
2 endoplasmic reticulum GO:0005783 9.28 XBP1 WFS1 PPP1R15B PPP1R15A KCNJ11 IER3IP1
3 protein phosphatase type 1 complex GO:0000164 9.26 PPP1R15B PPP1R15A
4 integral component of endoplasmic reticulum membrane GO:0030176 9.26 XBP1 WFS1 EIF2AK3 ATF6
5 inward rectifying potassium channel GO:0008282 9.16 KCNJ11 ABCC8

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

(show all 31)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.11 XBP1 RFX6 PTF1A GLIS3 ATF6 ATF4
2 glucose homeostasis GO:0042593 9.8 WFS1 RFX6 INS
3 response to unfolded protein GO:0006986 9.78 XBP1 EIF2AK3 DNAJC3 ATF6
4 regulation of insulin secretion GO:0050796 9.77 RFX6 KCNJ11 ABCC8
5 IRE1-mediated unfolded protein response GO:0036498 9.75 XBP1 WFS1 DNAJC3
6 cellular response to UV GO:0034644 9.74 EIF2S1 EIF2AK4 ATF4
7 endoplasmic reticulum unfolded protein response GO:0030968 9.71 XBP1 WFS1 EIF2AK3 ATF6
8 cellular response to glucose starvation GO:0042149 9.7 XBP1 EIF2AK3 ATF4
9 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0070059 9.69 XBP1 PPP1R15A ATF4
10 endocrine pancreas development GO:0031018 9.65 RFX6 EIF2AK3
11 positive regulation of protein localization to nucleus GO:1900182 9.65 INS EIF2AK3
12 positive regulation of long-term synaptic potentiation GO:1900273 9.64 INS EIF2AK4
13 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1902236 9.64 XBP1 WFS1
14 PERK-mediated unfolded protein response GO:0036499 9.63 EIF2S1 EIF2AK3 ATF4
15 regulation of translation GO:0006417 9.63 PPP1R15B PPP1R15A EIF2S1 EIF2AK4 EIF2AK3 DNAJC3
16 fatty acid homeostasis GO:0055089 9.62 XBP1 INS
17 positive regulation of phosphoprotein phosphatase activity GO:0032516 9.62 PPP1R15B PPP1R15A
18 cellular response to amino acid starvation GO:0034198 9.62 EIF2S1 EIF2AK4 EIF2AK3 ATF4
19 positive regulation of transcription by RNA polymerase I GO:0045943 9.61 EIF2AK3 ATF4
20 positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress GO:1990440 9.61 ATF6 ATF4
21 ER overload response GO:0006983 9.61 WFS1 PPP1R15B EIF2AK3
22 ATF6-mediated unfolded protein response GO:0036500 9.6 XBP1 ATF6
23 exocrine pancreas development GO:0031017 9.58 XBP1 PTF1A
24 negative regulation of PERK-mediated unfolded protein response GO:1903898 9.56 PPP1R15B PPP1R15A
25 negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation GO:1903912 9.55 PPP1R15B DNAJC3
26 regulation of translational initiation by eIF2 alpha phosphorylation GO:0010998 9.54 EIF2AK4 EIF2AK3
27 cellular response to cold GO:0070417 9.54 EIF2AK4 EIF2AK3 DNAJC3
28 eiF2alpha phosphorylation in response to endoplasmic reticulum stress GO:0036492 9.49 EIF2AK4 EIF2AK3
29 response to manganese-induced endoplasmic reticulum stress GO:1990737 9.43 EIF2S1 EIF2AK3 ATF4
30 negative regulation of translational initiation in response to stress GO:0032057 9.26 EIF2S1 EIF2AK4 EIF2AK3 ATF4
31 response to endoplasmic reticulum stress GO:0034976 9.17 WFS1 PPP1R15B PPP1R15A EIF2S1 EIF2AK3 DNAJC3

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 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.26 XBP1 RFX6 ATF6 ATF4
2 eukaryotic translation initiation factor 2alpha kinase activity GO:0004694 8.62 EIF2AK4 EIF2AK3

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

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9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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68 SNOMED-CT via HPO
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