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LEPRCH
MCID: DNH001
MIFTS: 62

Donohue Syndrome (LEPRCH)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Rare diseases, Skin diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Donohue Syndrome

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MalaCards integrated aliases for Donohue Syndrome:

Name: Donohue Syndrome 56 12 52 25 58 73 43 15 39 71
Leprechaunism 56 12 74 52 25 58 73 36 13 54
Leprechaunism Syndrome 25 29 6
Donohue's Syndrome 25
Leprch 73

Characteristics:

Orphanet epidemiological data:

58
leprechaunism
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: early childhood;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
death often in early infancy


HPO:

31
donohue syndrome:
Inheritance autosomal recessive inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases Fetal diseases
Anatomical: Skin diseases Endocrine diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Donohue Syndrome

About this section
Genetics Home Reference : 25 Donohue syndrome is a rare disorder characterized by severe insulin resistance, a condition in which the body's tissues and organs do not respond properly to the hormone insulin. Insulin normally helps regulate blood sugar levels by controlling how much sugar (in the form of glucose) is passed from the bloodstream into cells to be used as energy. Severe insulin resistance leads to problems with regulating blood sugar levels and affects the development and function of organs and tissues throughout the body. Severe insulin resistance underlies the varied signs and symptoms of Donohue syndrome. Individuals with Donohue syndrome are unusually small starting before birth, and affected infants experience failure to thrive, which means they do not grow and gain weight at the expected rate. Additional features that become apparent soon after birth include a lack of fatty tissue under the skin (subcutaneous fat); wasting (atrophy) of muscles; excessive body hair growth (hirsutism); multiple cysts on the ovaries in females; and enlargement of the nipples, genitalia, kidneys, heart, and other organs. Most affected individuals also have a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety. Distinctive facial features in people with Donohue syndrome include bulging eyes, thick lips, upturned nostrils, and low-set ears. Affected individuals develop recurrent, life-threatening infections beginning in infancy. Donohue syndrome is one of a group of related conditions described as inherited severe insulin resistance syndromes. These disorders, which also include Rabson-Mendenhall syndrome and type A insulin resistance syndrome, are considered part of a spectrum. Donohue syndrome represents the most severe end of the spectrum; most children with this condition do not survive beyond age 2.

MalaCards based summary : Donohue Syndrome, also known as leprechaunism, is related to pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities and acquired generalized lipodystrophy, and has symptoms including elfin facies and female breast hyperplasia. An important gene associated with Donohue Syndrome is INSR (Insulin Receptor), and among its related pathways/superpathways are Adherens junction and Insulin signaling pathway. The drugs Insulin, Globin Zinc and insulin have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and ovary, and related phenotypes are hyperkeratosis and postnatal growth retardation

Disease Ontology : 12 A syndrome that is characterized by protuberant and low-set ears, flaring nostrils, thick lips, enlarged secondary sex organs and overwhelming insulin resistance and has material basis in mutation within the INSR gene causing abnormalities in the insulin receptor.

NIH Rare Diseases : 52 Leprechaunism is a congenital (present from birth) condition characterized by extreme insulin resistance , pre- and postnatal growth delays, characteristic facial features, skin abnormalities, muscular hypotrophy (reduced muscle mass) and enlarged external genitalia in both males and females. The condition is caused by mutations in the insulin receptor gene (INSR ) gene. It is inherited in an autosomal recessive manner.

KEGG : 36 Leprechaunism (Donohue syndrome) is an autosomal recessive disorder of insulin-resistance characterized by intrauterine and postnatal growth retardation, acanthosis nigricans, lipoatrophy, and genitomegaly. The disease is known as leprechaunism because infants with the disease show an elf-like face and short stature.

UniProtKB/Swiss-Prot : 73 Leprechaunism: Represents the most severe form of insulin resistance syndrome, characterized by intrauterine and postnatal growth retardation and death in early infancy. Inheritance is autosomal recessive.

Wikipedia : 74 Donohue syndrome (also known as leprechaunism) is an extremely rare and severe genetic disorder.... more...

More information from OMIM: 246200
Sources

Related Diseases for Donohue Syndrome

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Diseases related to Donohue Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 151)
# Related Disease Score Top Affiliating Genes
1 pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities 32.1 INSR INS IGFBP3 IGF1
2 acquired generalized lipodystrophy 31.7 BSCL2 AGPAT2
3 fasting hypoglycemia 30.8 INSR IGF1
4 acanthosis nigricans 30.0 INSR INS IGF1R IGF1 BAIAP2L1
5 marasmus 30.0 INS IGFBP3 IGF1
6 hyperandrogenism 30.0 INSR INS IGFBP3 IGF1
7 hypoglycemia 29.4 INSR INS IGFBP3 IGF1 GCK
8 hyperinsulinemic hypoglycemia 29.3 INSR INS IGF1R GCK
9 insulin-like growth factor i 29.2 IRS1 INSR INS IGFBP3 IGF1R IGF1
10 polycystic ovary syndrome 29.2 IRS1 INSR INS IGFBP3 IGF1
11 hyperglycemia 29.1 IRS1 INSR INS IGF1R IGF1 GCK
12 endometrial cancer 28.8 INS IGFBP3 IGF1R IGF1 EGF AURKA
13 glucose intolerance 28.7 IRS1 INSR INS IGFBP3 IGF1 GCK
14 hyperinsulinism 28.6 IRS1 INSR INS IGFBP3 IGF1R IGF1
15 diabetes mellitus, noninsulin-dependent 26.4 IRS1 INSR INS IGFBP3 IGF1R IGF1
16 patterson pseudoleprechaunism syndrome 11.3
17 diabetes mellitus, insulin-resistant, with acanthosis nigricans 11.3
18 insulin-resistance type b 11.2
19 autosomal recessive disease 10.5
20 hypertrichosis 10.5
21 insr-related severe syndromic insulin resistance 10.4
22 hypertrophic cardiomyopathy 10.4
23 hypothalamic obesity 10.4 INS IGF1
24 pituitary infarct 10.3 INS IGF1
25 acidophil adenoma 10.3 INS IGF1
26 potter's syndrome 10.3 INS IGF1
27 sheehan syndrome 10.3 INS IGF1
28 pituitary apoplexy 10.3 INS IGF1
29 cutis laxa 10.3
30 cerebral meningioma 10.3 IGF1 EGF
31 skin tag 10.3 INS IGF1
32 slipped capital femoral epiphysis 10.2 IGFBP3 IGF1
33 diabetes mellitus, insulin-dependent, 20 10.2 INS IGF1
34 mammographic density 10.2 IGFBP3 IGF1
35 muscular atrophy 10.2
36 growth hormone deficiency 10.2
37 overgrowth syndrome 10.2
38 dowling-degos disease 1 10.1
39 keratosis 10.1
40 47,xyy 10.1
41 amelogenesis imperfecta, type ig 10.1 IGF1R IGF1 EGF
42 nerve compression syndrome 10.1 INS IGF1
43 retinal detachment 10.1
44 3-methylglutaconic aciduria, type iii 10.1
45 joint laxity, short stature, and myopia 10.1
46 myopia 10.1
47 mature cataract 10.1
48 diabetic encephalopathy 10.1 IRS1 INS IGF1
49 acid-labile subunit deficiency 10.0 IGFBP3 IGF1
50 prediabetes syndrome 10.0 IRS1 INS IGF1

Graphical network of the top 20 diseases related to Donohue Syndrome:



Diseases related to Donohue Syndrome
Sources

Symptoms & Phenotypes for Donohue Syndrome

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Human phenotypes related to Donohue Syndrome:

58 31 (show top 50) (show all 68)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperkeratosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000962
2 postnatal growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0008897
3 insulin resistance 58 31 hallmark (90%) Very frequent (99-80%) HP:0000855
4 severe intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0008846
5 postprandial hyperglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0011998
6 reduced subcutaneous adipose tissue 58 31 hallmark (90%) Very frequent (99-80%) HP:0003758
7 fasting hypoglycemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003162
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 hepatomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002240
10 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
11 hypertrophic cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001639
12 skeletal muscle atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003202
13 hyperinsulinemia 58 31 frequent (33%) Frequent (79-30%) HP:0000842
14 severe global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0011344
15 acanthosis nigricans 58 31 frequent (33%) Frequent (79-30%) HP:0000956
16 enlarged kidney 58 31 frequent (33%) Frequent (79-30%) HP:0000105
17 long penis 58 31 frequent (33%) Frequent (79-30%) HP:0000040
18 abdominal distention 58 31 frequent (33%) Frequent (79-30%) HP:0003270
19 clitoral hypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0008665
20 labial hypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000065
21 facial hypertrichosis 58 31 frequent (33%) Frequent (79-30%) HP:0002219
22 overgrowth of external genitalia 58 31 frequent (33%) Frequent (79-30%) HP:0003247
23 prominent nipples 58 31 frequent (33%) Frequent (79-30%) HP:0004405
24 recurrent infantile hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0004914
25 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
26 thick vermilion border 58 31 occasional (7.5%) Occasional (29-5%) HP:0012471
27 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
28 hypokalemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002900
29 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
30 nephrocalcinosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000121
31 protruding ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0000411
32 hyperaldosteronism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000859
33 hypercalciuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002150
34 pointed chin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000307
35 rectal prolapse 58 31 occasional (7.5%) Occasional (29-5%) HP:0002035
36 hyperextensible skin 58 31 occasional (7.5%) Occasional (29-5%) HP:0000974
37 wide nose 58 31 occasional (7.5%) Occasional (29-5%) HP:0000445
38 large hands 58 31 occasional (7.5%) Occasional (29-5%) HP:0001176
39 muscular hypotonia of the trunk 58 31 occasional (7.5%) Occasional (29-5%) HP:0008936
40 long foot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001833
41 enlarged ovaries 58 31 occasional (7.5%) Occasional (29-5%) HP:0100879
42 increased circulating renin level 58 31 occasional (7.5%) Occasional (29-5%) HP:0000848
43 central hypothyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0011787
44 megarectum 58 31 occasional (7.5%) Occasional (29-5%) HP:0025024
45 hypertrichosis 58 31 Very frequent (99-80%) HP:0000998
46 delayed skeletal maturation 31 HP:0002750
47 gingival overgrowth 31 HP:0000212
48 macrotia 31 HP:0000400
49 thick lower lip vermilion 31 HP:0000179
50 hypermelanotic macule 31 HP:0001034

Symptoms via clinical synopsis from OMIM:

56
Skin Nails Hair Skin:
hyperkeratosis
acanthosis nigricans
pachyderma

Head And Neck Ears:
low-set ears
large ears

Abdomen Liver:
hepatic fibrosis
cholestasis

Skeletal Hands:
large hands

Laboratory Abnormalities:
postprandial hyperglycemia
fasting hypoglycemia
elevated plasma insulin
absent anti-insulin receptor antibodies

Skeletal Feet:
large feet

Skeletal:
delayed bone age

Skin Nails Hair Nails:
dysplastic nails

Genitourinary Internal Genitalia Male:
leydig cell hyperplasia

Immunology:
frequent infections
decreased lymphatic tissue (tonsil, thymus, mesenteric nodes, peyer patches)

Abdomen Pancreas:
islets of langerhans hyperplasia

Genitourinary Internal Genitalia Female:
cystic ovaries

Neoplasia:
juvenile ovarian granulosa cell tumor

Growth Other:
postnatal growth retardation
severe failure to thrive
prenatal growth retardation

Endocrine Features:
hyperinsulinemia
precocious puberty

Head And Neck Face:
elfin facies
small face

Abdomen External Features:
abdominal distention

Chest Breasts:
prominent nipples
breast hyperplasia (female)

Head And Neck Mouth:
thick lips
large mouth
gingival hyperplasia

Muscle Soft Tissue:
muscle wasting
marked lack of adipose tissue

Head And Neck Eyes:
prominent eyes

Genitourinary External Genitalia Male:
large penis

Head And Neck Nose:
wide nostrils

Genitourinary External Genitalia Female:
large clitoris

Skin Nails Hair Hair:
hypertrichosis (body, face)

Clinical features from OMIM:

246200

UMLS symptoms related to Donohue Syndrome:


elfin facies, female breast hyperplasia

GenomeRNAi Phenotypes related to Donohue Syndrome according to GeneCards Suite gene sharing:

26 (show all 14)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.39 AURKA
2 Decreased viability GR00055-A-2 10.39 AURKA
3 Decreased viability GR00221-A-1 10.39 AURKA GCK IGF1R INSR IRS1
4 Decreased viability GR00221-A-2 10.39 AURKA GCK IGF1R INSR IRS1
5 Decreased viability GR00221-A-3 10.39 GCK IGF1R INSR
6 Decreased viability GR00221-A-4 10.39 AURKA GCK INSR
7 Decreased viability GR00231-A 10.39 AURKA
8 Decreased viability GR00249-S 10.39 AURKA
9 Decreased viability GR00301-A 10.39 IGF1R
10 Decreased viability GR00342-S-2 10.39 IGF1R IRS1
11 Decreased viability GR00342-S-3 10.39 IRS1
12 Decreased viability GR00386-A-1 10.39 IRS1
13 Decreased viability GR00402-S-2 10.39 AURKA IGF1R
14 Increased cell death in HCT116 cells GR00103-A-0 8.32 AURKA

MGI Mouse Phenotypes related to Donohue Syndrome:

45 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.26 AGPAT2 AURKA BAIAP2L1 BSCL2 EGF GCK
2 cardiovascular system MP:0005385 10.19 BAIAP2L1 BSCL2 GCK IGF1 IGF1R IGFBP3
3 endocrine/exocrine gland MP:0005379 10.19 AGPAT2 BSCL2 EGF GCK IGF1 IGF1R
4 cellular MP:0005384 10.18 AURKA BSCL2 GCK IGF1 IGF1R IGFBP3
5 homeostasis/metabolism MP:0005376 10.17 AGPAT2 BAIAP2L1 BSCL2 GCK IGF1 IGF1R
6 hematopoietic system MP:0005397 10.16 AGPAT2 AURKA BSCL2 GCK IGF1 IGF1R
7 adipose tissue MP:0005375 10.15 AGPAT2 BSCL2 IGF1 IGF1R IGFBP3 INS
8 immune system MP:0005387 10.06 AGPAT2 BSCL2 EGF IGF1 IGF1R INS
9 digestive/alimentary MP:0005381 9.99 AGPAT2 BSCL2 EGF IGF1R INS INSR
10 integument MP:0010771 9.91 AGPAT2 BSCL2 EGF IGF1 IGF1R IGFBP3
11 limbs/digits/tail MP:0005371 9.87 AGPAT2 BAIAP2L1 BSCL2 IGF1 IGF1R IGFBP3
12 liver/biliary system MP:0005370 9.86 AGPAT2 BSCL2 GCK IGF1R IGFBP3 INS
13 mortality/aging MP:0010768 9.85 AGPAT2 AURKA BAIAP2L1 BSCL2 GCK IGF1
14 muscle MP:0005369 9.43 IGF1 IGF1R IGFBP3 INS INSR IRS1
15 renal/urinary system MP:0005367 9.1 AGPAT2 BSCL2 GCK IGF1 INS INSR
Sources

Drugs & Therapeutics for Donohue Syndrome

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Drugs for Donohue Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Insulin, Globin Zinc Phase 2
2 insulin Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Efficacy of Leptin in Severe Insulin Resistance: A Pilot Study Completed NCT00027456 Phase 2 Leptin A-100

Search NIH Clinical Center for Donohue Syndrome

Cochrane evidence based reviews: donohue syndrome

Sources

Genetic Tests for Donohue Syndrome

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Genetic tests related to Donohue Syndrome:

# Genetic test Affiliating Genes
1 Leprechaunism Syndrome 29 INSR
Sources

Anatomical Context for Donohue Syndrome

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MalaCards organs/tissues related to Donohue Syndrome:

40
Skin, Eye, Ovary, Kidney, Heart, Breast, Pancreatic Islet
Sources

Publications for Donohue Syndrome

About this section

Articles related to Donohue Syndrome:

(show top 50) (show all 272)
# Title Authors PMID Year
1
Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance. 56 6 61 54
7815442 1994
2
A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents. 54 56 6 61
8326490 1993
3
Identification and functional assessment of novel and known insulin receptor mutations in five patients with syndromes of severe insulin resistance. 61 54 6
12970295 2003
4
Genotype-phenotype correlation in inherited severe insulin resistance. 54 61 6
12023989 2002
5
A mutation in the insulin receptor that impairs proreceptor processing but not insulin binding. 6 61 54
8188715 1994
6
Reduced mRNA and a nonsense mutation in the insulin-receptor gene produce heritable severe insulin resistance. 6 54 61
1315125 1992
7
An Arg for Gly substitution at position 31 in the insulin receptor, linked to insulin resistance, inhibits receptor processing and transport. 61 54 6
1730625 1992
8
Five mutant alleles of the insulin receptor gene in patients with genetic forms of insulin resistance. 6 54 61
2365819 1990
9
A nonsense mutation causing decreased levels of insulin receptor mRNA: detection by a simplified technique for direct sequencing of genomic DNA amplified by the polymerase chain reaction. 6 54 61
2300553 1990
10
INSR-Related Severe Syndromic Insulin Resistance 61 6
29369573 2018
11
Sequencing analysis of insulin receptor defects and detection of two novel mutations in INSR gene. 6 61
27896077 2014
12
Leprechaunism and homozygous nonsense mutation in the insulin receptor gene. 61 56
8105179 1993
13
Homozygous deletion of the human insulin receptor gene results in leprechaunism. 6 61
7693131 1993
14
Homozygous nonsense mutation in the insulin receptor gene in infant with leprechaunism. 61 6
8101305 1993
15
Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis. 6 61
1607067 1992
16
Substitution of arginine for histidine at position 209 in the alpha-subunit of the human insulin receptor. A mutation that impairs receptor dimerization and transport of receptors to the cell surface. 61 6
1657953 1991
17
Epidermal growth factor receptor defects in leprechaunism. A multiple growth factor-resistant syndrome. 61 56
2808704 1989
18
A leucine-to-proline mutation in the insulin receptor in a family with insulin resistance. 61 6
2479553 1989
19
Molecular defects in the insulin receptor in patients with leprechaunism and in their parents. 56 61
2569023 1989
20
Insulin receptor function in fibroblasts from patients with leprechaunism. Differential alterations in binding, autophosphorylation, kinase activity, and receptor-mediated internalization. 61 56
3049675 1988
21
Two mutant alleles of the insulin receptor gene in a patient with extreme insulin resistance. 6 61
2834824 1988
22
Improper expression of insulin receptors on fibroblasts from a leprechaun patient. 61 6
3280314 1988
23
Structural analysis of normal and mutant insulin receptors in fibroblasts cultured from families with leprechaunism. 61 56
3631076 1987
24
Leprechaunism: in vitro insulin action despite genetic insulin resistance. 61 56
3309859 1987
25
[A rare polydysmorphic syndrome: leprechaunism. Review of 49 cases reported in the literature]. 56 61
3322162 1987
26
Leprechaunism: an inherited defect in a high-affinity insulin receptor. 56 61
3883764 1985
27
Fibroblasts from a patient with leprechaunism are resistant to insulin, epidermal growth factor, and somatomedin C. 61 56
6286709 1982
28
Hepatic ultrastructure in leprechaunism. Hepatic ultrastructural evidence suggesting a syndrome with defective hepatic glucose release. 56 61
7179734 1982
29
Qualitative abnormalities in insulin binding in a patient with extreme insulin resistance: decreased sensitivity to alterations in temperature and pH. 61 56
7031672 1981
30
Glucose kinetics in leprechaunism: accelerated fasting due to insulin resistance. 61 56
6999010 1980
31
A case of leprechaunism with severe hyperinsulinemia. 61 56
6986080 1980
32
Primary defect of insulin receptors in skin fibroblasts cultured from an infant with leprechaunism and insulin resistance. 61 56
293690 1979
33
Insulin resistance due to a defect distal to the insulin receptor: demonstration in a patient with leprechaunism. 61 56
277948 1978
34
Leprechaunism. A report of two new cases. 56 61
5129536 1971
35
[Clinical picture of congenital dysendocrinic disease or leprechaunism]. 61 56
4991281 1970
36
Leprechaunism (Donohue's syndrome): a case report. 61 56
4886189 1969
37
Metabolic and chromosomal studies in leprechaunism. 56 61
5844952 1965
38
DYSTROPHIC CHANGES ASSOCIATED WITH LEPRECHAUNISM IN A MALE INFANT. 61 56
14065999 1963
39
[Leprechaunism (Donohue syndrome)]. 56 61
13928153 1963
40
Leprechaunism in a male infant. 56 61
14484402 1962
41
Leprechaunism. 56 61
13275976 1955
42
Leprechaunism: a euphemism for a rare familial disorder. 61 56
13212592 1954
43
Activation of glucose transport by a natural mutation in the human insulin receptor. 6
8419945 1993
44
Sustained regression of florid diabetic retinopathy in a patient with Donohue syndrome (leprechaunism). 54 61
19882513 2010
45
Downregulation of Wnt-mediated ROS generation is causally implicated in leprechaunism. 61 54
20033851 2010
46
Dental and craniofacial characteristics in a patient with leprechaunism treated with insulin-like growth factor-I. 54 61
18302477 2008
47
Two novel mutations in the insulin binding subunit of the insulin receptor gene without insulin binding impairment in a patient with Rabson-Mendenhall syndrome. 54 61
18411068 2008
48
Insulin effect on serum potassium and auto-inhibition of insulin secretion is intact in a patient with leprechaunism despite severe impairment of substrates metabolism. 54 61
17968975 2008
49
Some effect of metformin on insulin resistance in an infant with leprechaunism. 61 54
17172088 2006
50
[Leprechaunism: an inherited insulin resistance syndrome caused by the defect of insulin receptor]. 54 61
17166446 2006
Sources

Variations for Donohue Syndrome

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ClinVar genetic disease variations for Donohue Syndrome:

6 (show top 50) (show all 263) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 INSR NM_000208.4(INSR):c.167T>C (p.Ile56Thr)SNV Pathogenic 504474 rs1555689937 19:7267841-7267841 19:7267830-7267830
2 INSR NM_000208.4(INSR):c.3003_3012delinsGGAAG (p.Ser1001fs)indel Pathogenic 504475 rs1555735951 19:7126596-7126605 19:7126585-7126594
3 INSR NM_000208.4(INSR):c.632C>T (p.Thr211Ile)SNV Pathogenic 916551 19:7267376-7267376 19:7267365-7267365
4 INSR NM_000208.4(INSR):c.1459A>G (p.Lys487Glu)SNV Pathogenic 14680 rs121913136 19:7170572-7170572 19:7170561-7170561
5 INSR NM_000208.4(INSR):c.1177G>A (p.Gly393Arg)SNV Pathogenic 14681 rs267607184 19:7172392-7172392 19:7172381-7172381
6 INSR NM_000208.4(INSR):c.2095C>T (p.Gln699Ter)SNV Pathogenic 14682 rs121913137 19:7152873-7152873 19:7152862-7152862
7 INSR NM_000208.4(INSR):c.2770C>T (p.Arg924Ter)SNV Pathogenic 14686 rs387906538 19:7132241-7132241 19:7132230-7132230
8 INSR NM_000208.4(INSR):c.779T>C (p.Leu260Pro)SNV Pathogenic 14689 rs121913141 19:7184522-7184522 19:7184511-7184511
9 INSR NM_000208.4(INSR):c.707A>G (p.His236Arg)SNV Pathogenic 14693 rs121913145 19:7184594-7184594 19:7184583-7184583
10 INSR NM_000208.4(INSR):c.172G>A (p.Gly58Arg)SNV Pathogenic 14699 rs52836744 19:7267836-7267836 19:7267825-7267825
11 INSR NM_000208.4(INSR):c.164T>C (p.Val55Ala)SNV Pathogenic 14702 rs121913152 19:7267844-7267844 19:7267833-7267833
12 INSR NM_000208.4(INSR):c.338G>C (p.Arg113Pro)SNV Pathogenic 14703 rs121913153 19:7267670-7267670 19:7267659-7267659
13 INSR NM_000208.4(INSR):c.442A>T (p.Lys148Ter)SNV Pathogenic 14705 rs121913155 19:7267566-7267566 19:7267555-7267555
14 INSR NC_000019.10:g.(?_7112255)_(7249328_?)deldeletion Pathogenic 14706 19:7112255-7249328
15 INSR NM_000208.4(INSR):c.1316G>C (p.Trp439Ser)SNV Pathogenic 14710 rs121913158 19:7170715-7170715 19:7170704-7170704
16 INSR NM_000208.4(INSR):c.438C>G (p.Ile146Met)SNV Pathogenic 14711 rs121913159 19:7267570-7267570 19:7267559-7267559
17 INSR NM_000208.4(INSR):c.1372A>G (p.Asn458Asp)SNV Pathogenic 14714 rs121913160 19:7170659-7170659 19:7170648-7170648
18 INSR NM_000208.4(INSR):c.3034G>A (p.Val1012Met)SNV Conflicting interpretations of pathogenicity 14707 rs1799816 19:7125518-7125518 19:7125507-7125507
19 INSR NM_000208.4(INSR):c.2838C>G (p.Asp946Glu)SNV Conflicting interpretations of pathogenicity 211195 rs146588336 19:7132173-7132173 19:7132162-7132162
20 INSR NM_000208.4(INSR):c.2736G>A (p.Arg912=)SNV Conflicting interpretations of pathogenicity 211194 rs147125937 19:7132275-7132275 19:7132264-7132264
21 INSR NM_000208.4(INSR):c.2243C>T (p.Ser748Leu)SNV Conflicting interpretations of pathogenicity 211190 rs143523271 19:7150532-7150532 19:7150521-7150521
22 INSR NM_000208.4(INSR):c.2263C>T (p.Pro755Ser)SNV Conflicting interpretations of pathogenicity 796295 19:7150512-7150512 19:7150501-7150501
23 INSR NM_000208.4(INSR):c.190T>C (p.Leu64=)SNV Conflicting interpretations of pathogenicity 195041 rs144836032 19:7267818-7267818 19:7267807-7267807
24 INSR NM_000208.4(INSR):c.2295C>T (p.Gly765=)SNV Conflicting interpretations of pathogenicity 330462 rs142654992 19:7143074-7143074 19:7143063-7143063
25 INSR NM_000208.4(INSR):c.2388G>C (p.Arg796Ser)SNV Conflicting interpretations of pathogenicity 549552 rs78433961 19:7142981-7142981 19:7142970-7142970
26 INSR NM_000208.4(INSR):c.2117C>A (p.Ala706Asp)SNV Conflicting interpretations of pathogenicity 435518 rs142391704 19:7152851-7152851 19:7152840-7152840
27 INSR NM_000208.4(INSR):c.225C>T (p.Asp75=)SNV Conflicting interpretations of pathogenicity 435514 rs41352749 19:7267783-7267783 19:7267772-7267772
28 INSR NM_000208.4(INSR):c.2793G>A (p.Ala931=)SNV Conflicting interpretations of pathogenicity 739582 19:7132218-7132218 19:7132207-7132207
29 INSR NM_000208.4(INSR):c.624A>G (p.Arg208=)SNV Conflicting interpretations of pathogenicity 742862 19:7267384-7267384 19:7267373-7267373
30 INSR NM_000208.4(INSR):c.575G>A (p.Gly192Asp)SNV Conflicting interpretations of pathogenicity 743458 19:7267433-7267433 19:7267422-7267422
31 INSR NM_000208.4(INSR):c.2498G>A (p.Arg833Gln)SNV Uncertain significance 502299 rs777565396 19:7142871-7142871 19:7142860-7142860
32 INSR NM_000208.4(INSR):c.653-9T>CSNV Uncertain significance 592488 rs868296217 19:7184657-7184657 19:7184646-7184646
33 INSR NM_000208.4(INSR):c.3143G>A (p.Gly1048Asp)SNV Uncertain significance 631539 rs200921389 19:7125409-7125409 19:7125398-7125398
34 INSR NM_000208.4(INSR):c.921_923CAA[2] (p.Asn309del)short repeat Uncertain significance 631537 rs775724610 19:7184372-7184374 19:7184361-7184363
35 INSR NM_000208.4(INSR):c.*97A>GSNV Uncertain significance 893832 19:7116970-7116970 19:7116959-7116959
36 INSR NM_000208.4(INSR):c.*87C>TSNV Uncertain significance 894751 19:7116980-7116980 19:7116969-7116969
37 INSR NM_000208.4(INSR):c.4139A>G (p.Asn1380Ser)SNV Uncertain significance 892766 19:7117077-7117077 19:7117066-7117066
38 INSR NM_000208.4(INSR):c.4133G>C (p.Arg1378Pro)SNV Uncertain significance 892767 19:7117083-7117083 19:7117072-7117072
39 INSR NM_000208.4(INSR):c.3844A>G (p.Thr1282Ala)SNV Uncertain significance 893573 19:7117372-7117372 19:7117361-7117361
40 INSR NM_000208.4(INSR):c.3501C>T (p.Val1167=)SNV Uncertain significance 893864 19:7122653-7122653 19:7122642-7122642
41 INSR NM_000208.4(INSR):c.3023G>C (p.Cys1008Ser)SNV Uncertain significance 893894 19:7125529-7125529 19:7125518-7125518
42 INSR NM_000208.4(INSR):c.2848G>A (p.Val950Ile)SNV Uncertain significance 894288 19:7128960-7128960 19:7128949-7128949
43 INSR NM_000208.4(INSR):c.2829C>T (p.Tyr943=)SNV Uncertain significance 892834 19:7132182-7132182 19:7132171-7132171
44 INSR NM_000208.4(INSR):c.2739G>T (p.Leu913=)SNV Uncertain significance 893639 19:7132272-7132272 19:7132261-7132261
45 INSR NM_000208.4(INSR):c.2698G>A (p.Val900Ile)SNV Uncertain significance 893925 19:7132313-7132313 19:7132302-7132302
46 INSR NM_000208.4(INSR):c.2602C>T (p.His868Tyr)SNV Uncertain significance 892863 19:7141768-7141768 19:7141757-7141757
47 INSR NM_000208.4(INSR):c.2596G>A (p.Val866Ile)SNV Uncertain significance 892864 19:7141774-7141774 19:7141763-7141763
48 INSR NM_000208.4(INSR):c.2522G>A (p.Ser841Asn)SNV Uncertain significance 894351 19:7142847-7142847 19:7142836-7142836
49 INSR NM_000208.4(INSR):c.2380G>A (p.Glu794Lys)SNV Uncertain significance 892904 19:7142989-7142989 19:7142978-7142978
50 INSR NM_000208.4(INSR):c.2276G>A (p.Arg759Gln)SNV Uncertain significance 893980 19:7143093-7143093 19:7143082-7143082

UniProtKB/Swiss-Prot genetic disease variations for Donohue Syndrome:

73 (show all 25)
# Symbol AA change Variation ID SNP ID
1 INSR p.Val55Ala VAR_004080 rs121913152
2 INSR p.Gly58Arg VAR_004081 rs52836744
3 INSR p.Arg113Pro VAR_004082 rs121913153
4 INSR p.His236Arg VAR_004084 rs121913145
5 INSR p.Leu260Pro VAR_004085 rs121913141
6 INSR p.Gly393Arg VAR_004086 rs267607184
7 INSR p.Lys487Glu VAR_004088 rs121913136
8 INSR p.Ile146Met VAR_015539 rs121913159
9 INSR p.Trp439Ser VAR_015542 rs121913158
10 INSR p.Ala119Val VAR_015909 rs134747302
11 INSR p.Cys301Tyr VAR_015912
12 INSR p.Ser350Leu VAR_015914
13 INSR p.Ile925Thr VAR_015918
14 INSR p.Arg926Trp VAR_015919 rs911929963
15 INSR p.Thr937Met VAR_015920
16 INSR p.Arg1119Trp VAR_015925 rs122973067
17 INSR p.Arg1201Trp VAR_015930
18 INSR p.Glu1206Lys VAR_015932
19 INSR p.Leu120Gln VAR_031518
20 INSR p.Asn458Asp VAR_031521 rs121913160
21 INSR p.Ile56Thr VAR_079535 rs155568993
22 INSR p.Cys286Tyr VAR_079537
23 INSR p.Val657Phe VAR_079540 rs113540173
24 INSR p.Trp659Arg VAR_079541
25 INSR p.Tyr818Cys VAR_079542

Sources

Expression for Donohue Syndrome

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Search GEO for disease gene expression data for Donohue Syndrome.
Sources

Pathways for Donohue Syndrome

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Pathways related to Donohue Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Adherens junction hsa04520
2 Insulin signaling pathway hsa04910
3 Aldosterone-regulated sodium reabsorption hsa04960

Pathways related to Donohue Syndrome according to GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Super pathways Score Top Affiliating Genes
1
p70S6K Signaling 63
Show member pathways
 12.96 IRS1 INSR INS IGF1R IGF1 EGF
2
PI3K-Akt signaling pathway 36
Show member pathways
 12.9 IRS1 INSR INS IGF1R IGF1 EGF
3
Endometrial cancer 36
Show member pathways
 12.8 IRS1 INS IGF1R IGF1 EGF
4
Ras signaling pathway 36
Show member pathways
 12.67 INSR INS IGF1R IGF1 EGF
5
MAPK signaling pathway 36 1
12.64 INSR INS IGF1R IGF1 GCK EGF
6
Downstream signaling events of B Cell Receptor (BCR) 65
Show member pathways
 12.63 IRS1 INSR INS EGF
7
Glioma 36
Show member pathways
 12.58 IRS1 IGF1R IGF1 EGF
8
Regulation of lipid metabolism Insulin signaling-generic cascades 22
Show member pathways
 12.53 IRS1 INSR INS IGFBP3 IGF1R IGF1
9
Development Dopamine D2 receptor transactivation of EGFR 22
Show member pathways
 12.49 IRS1 IGF1R IGF1 EGF
10
Angiopoietin Like Protein 8 Regulatory Pathway 1
Show member pathways
 12.44 IRS1 INSR INS IGF1R
11
mTOR signaling pathway (KEGG) 36
Show member pathways
 12.42 IRS1 INSR INS IGF1R IGF1
12
AMP-activated Protein Kinase (AMPK) Signaling 1
Show member pathways
 12.4 IRS1 INSR INS IGF1R IGF1
13
Phospholipase D signaling pathway 36
Show member pathways
 12.35 INSR INS EGF AGPAT2
14
Development IGF-1 receptor signaling 22
Show member pathways
 12.34 IRS1 IGFBP3 IGF1R IGF1
15
G-protein signaling RAC1 in cellular process 22
Show member pathways
 12.3 INSR IGF1R IGF1 EGF
16
Oocyte meiosis 36
Show member pathways
 12.3 INS IGF1R IGF1 AURKA
17
Translation Non-genomic (rapid) action of Androgen Receptor 22
Show member pathways
 12.25 IRS1 IGF1R IGF1 EGF
18
Development Ligand-independent activation of ESR1 and ESR2 22
Show member pathways
 12.2 IRS1 INSR IGF1R IGF1 EGF
19
Apoptosis and survival Caspase cascade 22
Show member pathways
 12.13 IRS1 IGF1R IGF1
20
AMPK Enzyme Complex Pathway 63
Show member pathways
 12.12 IRS1 INSR INS
21
MicroRNAs in cardiomyocyte hypertrophy 1
Show member pathways
 12.08 IGF1R IGF1 EGF
22
Tyrosine Kinases / Adaptors 4
12.07 IRS1 INSR IGF1R EGF
23
Autophagy - animal 36
12 IRS1 INS IGF1R
24
Glucose / Energy Metabolism 4
11.99 IRS1 INSR INS IGFBP3 IGF1R BSCL2
25
Embryonic and Induced Pluripotent Stem Cells and Lineage-specific Markers 64
11.98 INS IGF1 EGF
26
Longevity regulating pathway 36
Show member pathways
 11.98 IRS1 INSR INS IGF1R IGF1
27
Hepatic ABC Transporters 63
Show member pathways
 11.97 INSR INS IGF1R GCK
28
Glioblastoma Multiforme 63
11.9 IGF1R IGF1 EGF
29
Insulin resistance 36
Show member pathways
 11.89 IRS1 INSR INS
30
Adipogenesis 1
11.89 IRS1 INS IGF1 BSCL2 AGPAT2
31
Senescence and Autophagy in Cancer 1
11.86 INS IGFBP3 IGF1R IGF1
32
Type II diabetes mellitus 36 1
Show member pathways
 11.81 IRS1 INSR INS GCK
33
Mesenchymal Stem Cells and Lineage-specific Markers 64
11.79 INS IGFBP3 IGF1 EGF
34
HIF-1 signaling pathway 36
11.69 INSR INS IGF1R IGF1 EGF
35
G-protein signaling_RhoA regulation pathway 22
11.66 INSR IGF1R IGF1 EGF
36
AGE/RAGE pathway 1
11.64 IRS1 INSR INS
37
Regulation of lipolysis in adipocytes 36
11.56 IRS1 INSR INS
38
Differentiation Pathway 1
11.49 INS IGF1 EGF
39
Ovarian steroidogenesis 36
11.47 INSR INS IGF1R IGF1
40
Insulin Pathway 1
11.43 IRS1 INSR INS
41
Signaling events mediated by PTP1B 1
11.43 IRS1 INSR INS EGF
42
Signaling events mediated by TCPTP 1
Show member pathways
 11.41 INSR INS EGF
43
Factors and pathways affecting insulin-like growth factor (IGF1)-Akt signaling 1
11.26 IRS1 IGF1R IGF1
44
FoxO signaling pathway 36
Show member pathways
 11.24 IRS1 INSR INS IGF1R IGF1 EGF
45
Aldosterone-regulated sodium reabsorption 36
11.19 IRS1 INSR INS IGF1
46
IGF1 pathway 1
11.16 IRS1 IGF1R
47
EGFR Transactivation by Gastrin 65
Show member pathways
 11.16 IGF1R IGF1 EGF
48
Nanoparticle triggered autophagic cell death 1
11.08 INSR INS
49
Transcription factor regulation in adipogenesis 1
11.04 IRS1 INSR
50
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) 65
11.02 IGFBP3 IGF1
Sources

GO Terms for Donohue Syndrome

About this section

Cellular components related to Donohue Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin-like growth factor ternary complex GO:0042567 9.26 IGFBP3 IGF1
2 alphav-beta3 integrin-IGF-1-IGF1R complex GO:0035867 9.16 IGF1R IGF1
3 insulin-like growth factor binding protein complex GO:0016942 8.96 IGFBP3 IGF1
4 insulin receptor complex GO:0005899 8.8 IRS1 INSR IGF1R

Biological processes related to Donohue Syndrome according to GeneCards Suite gene sharing:

(show all 29)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell proliferation GO:0008284 9.97 IRS1 INSR INS IGF1R IGF1 EGF
2 positive regulation of cell migration GO:0030335 9.88 INSR INS IGF1R IGF1 EGF
3 protein autophosphorylation GO:0046777 9.82 INSR IGF1R AURKA
4 peptidyl-tyrosine phosphorylation GO:0018108 9.8 INSR IGF1R EGF
5 activation of MAPK activity GO:0000187 9.79 INSR IGF1 EGF
6 cellular response to insulin stimulus GO:0032869 9.77 IRS1 INSR GCK
7 positive regulation of protein kinase B signaling GO:0051897 9.77 IRS1 INSR INS IGF1R EGF
8 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.76 INSR INS IGF1R IGF1
9 phosphatidylinositol-mediated signaling GO:0048015 9.73 IRS1 IGF1R IGF1
10 insulin receptor signaling pathway GO:0008286 9.73 IRS1 INSR INS IGF1R
11 phosphatidylinositol 3-kinase signaling GO:0014065 9.71 IRS1 IGF1R IGF1
12 activation of protein kinase B activity GO:0032148 9.7 INSR INS IGF1
13 positive regulation of glycolytic process GO:0045821 9.69 INSR INS IGF1
14 glucose homeostasis GO:0042593 9.65 IRS1 INSR INS IGF1R GCK
15 positive regulation of receptor internalization GO:0002092 9.64 INSR EGF
16 positive regulation of insulin receptor signaling pathway GO:0046628 9.63 IRS1 INS
17 positive regulation of MAPK cascade GO:0043410 9.63 INSR INS IGFBP3 IGF1R IGF1 EGF
18 negative regulation of gluconeogenesis GO:0045721 9.62 INS GCK
19 negative regulation of lipid catabolic process GO:0050995 9.62 INS BSCL2
20 positive regulation of glucose import GO:0046326 9.62 IRS1 INSR INS IGF1
21 amyloid-beta clearance GO:0097242 9.61 INSR IGF1R
22 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.6 IGFBP3 IGF1
23 neuron projection maintenance GO:1990535 9.58 INSR INS
24 dendritic spine maintenance GO:0097062 9.58 INSR IGF1R
25 insulin-like growth factor receptor signaling pathway GO:0048009 9.58 IRS1 IGF1R IGF1
26 positive regulation of respiratory burst GO:0060267 9.57 INSR INS
27 positive regulation of protein complex disassembly GO:0043243 9.55 INSR IGF1R
28 positive regulation of mitotic nuclear division GO:0045840 9.35 INSR INS IGF1 EGF AURKA
29 positive regulation of glycogen biosynthetic process GO:0045725 9.02 IRS1 INSR INS IGF1 GCK

Molecular functions related to Donohue Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin-like growth factor binding GO:0005520 9.48 IGFBP3 IGF1R
2 cadherin binding involved in cell-cell adhesion GO:0098641 9.46 PDLIM1 BAIAP2L1
3 insulin receptor substrate binding GO:0043560 9.43 INSR IGF1R
4 phosphatidylinositol 3-kinase binding GO:0043548 9.43 IRS1 INSR IGF1R
5 insulin-like growth factor II binding GO:0031995 9.4 INSR IGFBP3
6 insulin binding GO:0043559 9.37 INSR IGF1R
7 insulin-like growth factor I binding GO:0031994 9.33 INSR IGFBP3 IGF1R
8 insulin-activated receptor activity GO:0005009 9.32 INSR IGF1R
9 insulin receptor binding GO:0005158 9.26 IRS1 INS IGF1R IGF1
10 insulin-like growth factor receptor binding GO:0005159 8.92 IRS1 INSR INS IGF1
Sources

Sources for Donohue Syndrome

About this section
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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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