LARS
MCID: LRN002
MIFTS: 63

Laron Syndrome (LARS)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Muscle diseases, Rare diseases
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Aliases & Classifications for Laron Syndrome

MalaCards integrated aliases for Laron Syndrome:

Name: Laron Syndrome 57 11 19 42 58 73 53 43 14 38 71 75
Growth Hormone Insensitivity Syndrome 57 19 42 58 73
Growth Hormone Receptor Deficiency 57 19 42 58 73
Laron Dwarfism 57 19 42 73 12
Laron-Type Isolated Somatotropin Defect 11 42 28 5
Pituitary Dwarfism Ii 57 19 42 73
Primary Growth Hormone Resistance 19 42 58
Laron-Type Dwarfism 42 58 75
Primary Growth Hormone Insensitivity 19 58
Laron Type Pituitary Dwarfism I 19 73
Primary Gh Resistance 42 58
Short Stature Due to a Defect in Growth Hormone Receptor or Post-Receptor Pathway 58
Short Stature Due to Growth Hormone Resistance 58
Complete Growth Hormone Insensitivity 58
Growth Hormone Receptor Defect 42
Laron-Type Pituitary Dwarfism 42
Laron-Type Short Stature 42
Primary Gh Insensitivity 58
Severe Gh Insensitivity 42
Gh Receptor Deficiency 58
Gh-R Deficiency 42
Ghis 58
Lars 73

Characteristics:


Inheritance:

Autosomal recessive 58 57

Prevelance:

1-9/1000000 (Europe) 1-9/100000 (China) 58

Age Of Onset:

Infancy,Neonatal 58

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
distorted sex ratio (19f:2m) in loja province ecuador cases.


Classifications:

Orphanet: 58  
Rare endocrine diseases


Summaries for Laron Syndrome

MedlinePlus Genetics: 42 Laron syndrome is a rare form of short stature that results from the body's inability to use growth hormone, a substance produced by the brain's pituitary gland that helps promote growth. Affected individuals are close to normal size at birth, but they experience slow growth from early childhood that results in very short stature. If the condition is not treated, adult males typically reach a maximum height of about 4.5 feet; adult females may be just over 4 feet tall.Other features of untreated Laron syndrome include reduced muscle strength and endurance, low blood sugar levels (hypoglycemia) in infancy, small genitals and delayed puberty, hair that is thin and fragile, and dental abnormalities. Many affected individuals have a distinctive facial appearance, including a protruding forehead, a sunken bridge of the nose (saddle nose), and a blue tint to the whites of the eyes (blue sclerae). Affected individuals have short limbs compared to the size of their torso, as well as small hands and feet. Adults with this condition tend to develop obesity. However, the signs and symptoms of Laron syndrome vary, even among affected members of the same family.Studies suggest that people with Laron syndrome have a significantly reduced risk of cancer and type 2 diabetes. Affected individuals appear to develop these common diseases much less frequently than their unaffected relatives, despite having obesity (a risk factor for both cancer and type 2 diabetes). However, people with Laron syndrome do not seem to have an increased lifespan compared with their unaffected relatives.

MalaCards based summary: Laron Syndrome, also known as growth hormone insensitivity syndrome, is related to isolated growth hormone deficiency and isolated growth hormone deficiency, type ia. An important gene associated with Laron Syndrome is GHR (Growth Hormone Receptor), and among its related pathways/superpathways are TGF-Beta Pathway and Akt Signaling. The drugs Mecasermin and Hormones have been mentioned in the context of this disorder. Affiliated tissues include pituitary, bone and subthalamic nucleus, and related phenotypes are failure to thrive and delayed skeletal maturation

Orphanet 58 Laron syndrome: Laron syndrome is a congenital disorder characterized by marked short stature associated with normal or high serum growth hormone (GH) and low serum insulin-like growth factor-1 (IGF-I) levels which fail to rise after exogenous GH administration.

Growth hormone insensitivity syndrome: Growth hormone insensitivity syndrome (GHIS) is a group of diseases characterized by marked short stature associated with normal or elevated growth hormone (GH) concentrations, which fail to respond to exogenous GH administration. GHIS comprises growth delay due to IGF-1 deficiency, growth delay due to IGF-1 resistance, Laron syndrome, short stature due to STAT5b deficiency and primary acid-labile subunit (ALS) deficiency (see these terms).

OMIM®: 57 Laron syndrome is an autosomal recessive disorder characterized by marked short stature that results from failure to generate insulin-like growth factor I (IGF1; 147440) in response to growth hormone (GH; 139250). GH levels are normal or increased. The disorder is caused by dysfunction of the growth hormone receptor. A Laron syndrome-like phenotype associated with immunodeficiency (245590) is caused by a postreceptor defect, i.e., mutation in the STAT5B gene (604260). Patients with mutations in the GHR gene that cause only partial insensitivity to growth hormone have a form of short stature (604271). (262500) (Updated 08-Dec-2022)

GARD: 19 Laron syndrome is a condition that occurs when the body is unable to utilize growth hormone. It is primarily characterized by short stature. Other signs and symptoms vary but may include reduced muscle strength and endurance; hypoglycemia in infancy; delayed puberty; short limbs (arms and legs); and obesity. It is often caused by changes in the GHR gene and is inherited in an autosomal recessive manner.

Disease Ontology: 11 A syndrome characterized by marked short stature with normal or high serum growth hormone and low serum insulin-like growth factor-1 levels that has material basis in homozygous or compound heterozygous mutation in GHR on chromosome 5p13-p12.

UniProtKB/Swiss-Prot: 73 A severe form of growth hormone insensitivity characterized by growth impairment, short stature, dysfunctional growth hormone receptor, and failure to generate insulin-like growth factor I in response to growth hormone.

Wikipedia: 75 Laron syndrome (LS), also known as growth hormone insensitivity or growth hormone receptor deficiency... more...

Related Diseases for Laron Syndrome

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

(show top 50) (show all 242)
# Related Disease Score Top Affiliating Genes
1 isolated growth hormone deficiency 30.5 IGF1 GHRHR GH1
2 isolated growth hormone deficiency, type ia 30.1 IGFBP3 IGF1 GHRHR GHR GH1
3 glucose intolerance 30.1 IGFBP1 IGF1 GH1 ADIPOQ
4 acid-labile subunit deficiency 30.0 IGFBP3 IGFALS IGF2 IGF1
5 adult syndrome 29.9 IGF2 IGF1 ADIPOQ
6 silver-russell syndrome 1 29.5 IGFBP3 IGFALS IGF2 IGF1
7 hypoglycemia 29.5 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1 GHR
8 insulin-like growth factor i 29.4 LEPQTL1 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2
9 hypothyroidism 29.4 STAT1 LEPQTL1 IGFBP3 IGF1 GHR GH1
10 hypopituitarism 29.3 IGFBP3 IGF1 GHRHR GHR GH1
11 hyperandrogenism 29.3 IGFBP3 IGFBP1 IGF2 IGF1 GH1 ADIPOQ
12 type 1 diabetes mellitus 28.5 LEPQTL1 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1
13 body mass index quantitative trait locus 11 28.4 STAT1 SIRT1 LEPQTL1 IGFBP3 IGFBP2 IGFBP1
14 hyperinsulinism 28.3 LEPQTL1 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1
15 diabetes mellitus 28.3 SIRT1 MIR132 IGFBP3 IGFBP2 IGFBP1 IGF2
16 type 2 diabetes mellitus 28.2 STAT1 SIRT1 LEPQTL1 IGFBP3 IGFBP2 IGFBP1
17 acromegaly 28.2 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1 GHRHR
18 osteoporosis 28.0 STAT1 SIRT1 LEPQTL1 IGFBP3 IGFBP2 IGFBP1
19 prostate cancer 27.5 STAT5B STAT1 SIRT1 IGFBP3 IGFBP2 IGFBP1
20 growth hormone insensitivity syndrome with immune dysregulation 2, autosomal dominant 11.8
21 growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive 11.6
22 growth hormone insensitivity syndrome with immune dysregulation 1 11.4
23 growth hormone insensitivity syndrome with immune dysregulation 2 11.4
24 growth hormone insensitivity, partial 11.4
25 laron syndrome with immunodeficiency 11.2
26 skin creases, congenital symmetric circumferential, 1 11.1
27 infantile liver failure syndrome 1 11.0
28 rectal benign neoplasm 10.5
29 rectum cancer 10.5
30 growth hormone deficiency 10.4
31 synovitis 10.3
32 bowel dysfunction 10.2
33 pineal hyperplasia, insulin-resistant diabetes mellitus, and somatic abnormalities 10.2 IGFBP3 IGF1
34 pseudovaginal perineoscrotal hypospadias 10.2
35 penis agenesis 10.2
36 sheehan syndrome 10.2 IGF1 GH1
37 hypothalamic disease 10.2 IGF1 GH1
38 precocious puberty 10.2
39 hypothyroidism, congenital, nongoitrous, 4 10.2 IGF1 GH1
40 fanconi anemia, complementation group a 10.2
41 leptin deficiency or dysfunction 10.2
42 pituitary adenoma 1, multiple types 10.2 IGFBP3 IGF1 GH1
43 empty sella syndrome 10.2 IGFBP3 IGF1 GH1
44 acanthosis nigricans 10.2 IGF1 GH1 ADIPOQ
45 skin tag 10.2 IGFBP3 IGF1
46 hyperprolactinemia 10.1 STAT5B IGF1 GH1
47 functioning pituitary adenoma 10.1 MIR132 IGF1 GH1
48 hypercholesterolemia, familial, 1 10.1
49 deficiency anemia 10.1
50 retroperitoneal hemangiopericytoma 10.1 IGF2 IGF1

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



Diseases related to Laron Syndrome

Symptoms & Phenotypes for Laron Syndrome

Human phenotypes related to Laron Syndrome:

58 30 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001508
2 delayed skeletal maturation 58 30 Very rare (1%) Very frequent (99-80%)
Frequent (79-30%)
HP:0002750
3 abnormal facial shape 58 30 Hallmark (90%) Very frequent (99-80%)
Very frequent (99-80%)
HP:0001999
4 microcephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000252
5 short stature 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0004322
6 everted lower lip vermilion 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000232
7 microdontia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000691
8 micrognathia 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000347
9 delayed eruption of teeth 58 30 Frequent (33%) Very frequent (99-80%)
Frequent (79-30%)
HP:0000684
10 hypercholesterolemia 58 30 Hallmark (90%) Occasional (29-5%)
Very frequent (99-80%)
HP:0003124
11 high forehead 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000348
12 truncal obesity 58 30 Occasional (7.5%) Very frequent (99-80%)
Occasional (29-5%)
HP:0001956
13 aplasia/hypoplasia involving the nose 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0009924
14 severe short stature 58 30 Very rare (1%) Very frequent (99-80%)
HP:0003510
15 insulin resistance 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0000855
16 hypoplastic nasal bridge 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0005281
17 tooth agenesis 30 Hallmark (90%) HP:0009804
18 type ii diabetes mellitus 58 30 Frequent (33%) Frequent (79-30%)
HP:0005978
19 delayed puberty 58 30 Frequent (33%) Frequent (79-30%)
HP:0000823
20 hypoglycemia 58 30 Frequent (33%) Frequent (79-30%)
Frequent (79-30%)
HP:0001943
21 short toe 58 30 Frequent (33%) Frequent (79-30%)
HP:0001831
22 motor delay 58 30 Frequent (33%) Frequent (79-30%)
HP:0001270
23 brachydactyly 58 30 Frequent (33%) Frequent (79-30%)
HP:0001156
24 fine hair 58 30 Frequent (33%) Frequent (79-30%)
HP:0002213
25 hypoplasia of penis 58 30 Frequent (33%) Frequent (79-30%)
Frequent (79-30%)
HP:0008736
26 abnormality of the elbow 58 30 Frequent (33%) Frequent (79-30%)
HP:0009811
27 underdeveloped supraorbital ridges 58 30 Frequent (33%) Frequent (79-30%)
HP:0009891
28 intellectual disability 58 30 Occasional (7.5%) Occasional (29-5%)
Occasional (29-5%)
HP:0001249
29 hearing impairment 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000365
30 abnormality of the nail 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001597
31 immunodeficiency 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002721
32 hypohidrosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000966
33 diabetes insipidus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000873
34 prematurely aged appearance 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0007495
35 depressed nasal ridge 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000457
36 large fontanelles 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000239
37 osteoarthritis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002758
38 high pitched voice 58 30 Occasional (7.5%) Occasional (29-5%)
Occasional (29-5%)
HP:0001620
39 blue sclerae 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000592
40 hypogonadism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000135
41 decreased serum insulin-like growth factor 1 30 Very rare (1%) HP:0030353
42 diabetes mellitus 58 Frequent (79-30%)
43 abnormality of the skeletal system 58 Frequent (79-30%)
44 abnormal skull morphology 58 Occasional (29-5%)
45 reduced number of teeth 58 Very frequent (99-80%)
46 abnormality of the mouth 58 Very frequent (99-80%)
47 abnormality of the endocrine system 58 Very frequent (99-80%)
48 limb undergrowth 30 HP:0009826
49 abnormal joint morphology 30 HP:0001367
50 short long bone 30 HP:0003026

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
Endocrine Features:
delayed menarche
target resistance to the action of gh

Skeletal:
delayed bone age
markedly advanced osseous maturation for height and age

Skeletal Limbs:
short limbs
limited elbow extensibility
acrohypoplasia

Growth Height:
marked short stature

Skeletal Pelvis:
hip degeneration

Head And Neck Face:
small facies

Voice:
high-pitched voice

Head And Neck Eyes:
blue sclerae (in some patients)

Growth Other:
clinical hyposomatotropism
normal body proportions in childhood
childlike body proportions in adults
greater deviation of stature than head size

Laboratory Abnormalities:
failure to generate somatomedin (or insulinlike growth factor, igf1) in response to growth hormone
normal or increased levels of gh
low igf1 despite normal or increased levels of gh

Clinical features from OMIM®:

262500 (Updated 08-Dec-2022)

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

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Reduced mammosphere formation GR00396-S 9.1 GHR IGF1 IGF2 IGFBP3 IL18R1 STAT1

MGI Mouse Phenotypes related to Laron Syndrome:

45 (show all 12)
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 10.18 ADIPOQ GH1 GHR IGF2 IGFBP1 IGFBP2
2 homeostasis/metabolism MP:0005376 10.18 ADIPOQ CFI GH1 GHR GHRHR IGF1
3 renal/urinary system MP:0005367 10.16 ADIPOQ CFI GH1 GHR IGF1 IGF2
4 adipose tissue MP:0005375 10.09 ADIPOQ CFI GH1 GHR GHRHR IGF1
5 endocrine/exocrine gland MP:0005379 10.07 ADIPOQ GH1 GHR GHRHR IGF1 IGF2
6 immune system MP:0005387 10.07 ADIPOQ CFI GH1 GHR GHRHR IGF1
7 limbs/digits/tail MP:0005371 10.06 GHR GHRHR IGF1 IGF2 IGFALS IGFBP3
8 cardiovascular system MP:0005385 10.06 ADIPOQ GH1 GHR GHRHR IGF1 IGF2
9 muscle MP:0005369 10.04 ADIPOQ GHR IGF1 IGF2 IGFBP3 SIRT1
10 skeleton MP:0005390 9.81 ADIPOQ GHR GHRHR IGF1 IGF2 IGFALS
11 hematopoietic system MP:0005397 9.73 ADIPOQ CFI GH1 GHR GHRHR IGF1
12 integument MP:0010771 9.28 ADIPOQ GHR GHRHR IGF1 IGF2 IGFBP3

Drugs & Therapeutics for Laron Syndrome

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


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Mecasermin Approved, Investigational Phase 2, Phase 3 68562-41-4
2 Hormones Phase 2, Phase 3
3 Insulin, Globin Zinc Phase 2, Phase 3
4
Insulin Phase 2, Phase 3
5 Mitogens Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 IGF-I/IGFBP-3 Therapy in Children and Adolescents With Growth Hormone Insenitivity Syndrome (GHIS) Such as Laron Syndrome Completed NCT00368173 Phase 2, Phase 3 rhIGF-I/rhIGFBP-3
2 A Study of the Long-Term Human Recombinant Insulin-Like Growth Factor-1 (rhIGF-1) Treatment in Children With Short Stature Due to Growth Hormone Insensitivity Syndrome (GHIS) Completed NCT00571727 Phase 2, Phase 3 mecasermin

Search NIH Clinical Center for Laron Syndrome

Cochrane evidence based reviews: laron syndrome

Genetic Tests for Laron Syndrome

Genetic tests related to Laron Syndrome:

# Genetic test Affiliating Genes
1 Laron-Type Isolated Somatotropin Defect 28 GHR

Anatomical Context for Laron Syndrome

Organs/tissues related to Laron Syndrome:

MalaCards : Pituitary, Bone, Subthalamic Nucleus, Prostate, Heart, Liver, Breast

Publications for Laron Syndrome

Articles related to Laron Syndrome:

(show top 50) (show all 1870)
# Title Authors PMID Year
1
Diverse growth hormone receptor gene mutations in Laron syndrome. 53 62 57 5
8488849 1993
2
The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador. 62 57 5
2233903 1990
3
Laron dwarfism and mutations of the growth hormone-receptor gene. 62 57 5
2779634 1989
4
Primary growth hormone (GH) insensitivity and insulin-like growth factor deficiency caused by novel compound heterozygous mutations of the GH receptor gene: genetic and functional studies of simple and compound heterozygous states. 53 62 5
17405847 2007
5
An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes. 53 62 5
17148568 2007
6
Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958-2003. 53 62 57
15001582 2004
7
Heterozygous nonsense mutation in exon 3 of the growth hormone receptor (GHR) in severe GH insensitivity (Laron syndrome) and the issue of the origin and function of the GHRd3 isoform. 53 62 5
12679461 2003
8
Therapy for 6.5-7.5 years with recombinant insulin-like growth factor I in children with growth hormone insensitivity syndrome: a clinical research center study. 53 62 57
11297575 2001
9
Recombinant human insulin-like growth factor I has significant anabolic effects in adults with growth hormone receptor deficiency: studies on protein, glucose, and lipid metabolism. 53 62 57
10999782 2000
10
Growth hormone receptor deficiency in Ecuador. 53 62 57
10599699 1999
11
Four contiguous amino acid substitutions, identified in patients with Laron syndrome, differently affect the binding affinity and intracellular trafficking of the growth hormone receptor. 53 62 5
9851797 1998
12
Normal intelligence with severe insulin-like growth factor I deficiency due to growth hormone receptor deficiency: a controlled study in a genetically homogeneous population. 53 62 5
9626125 1998
13
A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). 53 62 57
9371826 1997
14
Prolonged treatment with recombinant insulin-like growth factor-I in children with growth hormone insensitivity syndrome--a clinical research center study. GHIS Collaborative Group. 53 62 57
8784089 1996
15
A homozygous splice site mutation affecting the intracellular domain of the growth hormone (GH) receptor resulting in Laron syndrome with elevated GH-binding protein. 53 62 57
8626815 1996
16
Facial morphometry of Ecuadorian patients with growth hormone receptor deficiency/Laron syndrome. 53 62 57
7815422 1994
17
A single amino acid substitution in the exoplasmic domain of the human growth hormone (GH) receptor confers familial GH resistance (Laron syndrome) with positive GH-binding activity by abolishing receptor homodimerization. 53 62 5
8137822 1994
18
Lack of hormone binding in COS-7 cells expressing a mutated growth hormone receptor found in Laron dwarfism. 53 62 5
8450064 1993
19
Mutation creating a new splice site in the growth hormone receptor genes of 37 Ecuadorean patients with Laron syndrome. 53 62 5
1284474 1992
20
Effects of the infusion of insulin-like growth factor I in a child with growth hormone insensitivity syndrome (Laron dwarfism). 53 62 57
2023608 1991
21
Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. 62 57
21325617 2011
22
Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction. 62 5
15001620 2004
23
Clinical, biochemical and molecular investigations of three Taiwanese children with Laron syndrome. 62 5
15055350 2004
24
Are adult patients with Laron syndrome osteopenic? A comparison between dual-energy X-ray absorptiometry and volumetric bone densities. 62 57
14557426 2003
25
Phenotype: genotype relationships in growth hormone insensitivity syndrome. 62 57
9360502 1997
26
Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. 62 57
9024266 1997
27
Clinical, biochemical, and molecular investigations of a genetic isolate of growth hormone insensitivity (Laron's syndrome). 53 57
9024234 1997
28
Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism. 62 57
1349669 1992
29
Defective membrane expression of human growth hormone (GH) receptor causes Laron-type GH insensitivity syndrome. 62 5
1719554 1991
30
Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein. 62 57
1934534 1991
31
Recurrent nonsense mutations in the growth hormone receptor from patients with Laron dwarfism. 62 5
1999489 1991
32
Correction and withdrawal of conclusion--a child with phenotypic Laron dwarfism and normal somatomedin levels. 62 57
2288600 1990
33
High-affinity serum growth-hormone-binding protein, absent in Laron-type dwarfism, is diminished in heterozygous parents. 62 57
2074091 1990
34
Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. 62 5
2813379 1989
35
A child with phenotypic Laron dwarfism and normal somatomedin levels. 62 57
2725626 1989
36
A child with phenotypic Laron dwarfism and normal somatomedin levels. 62 57
2913494 1989
37
Chromosome mapping of the growth hormone receptor gene in man and mouse. 62 57
2776481 1989
38
Effect of acute administration of insulin-like growth factor I in patients with Laron-type dwarfism. 62 57
2903379 1988
39
Growth hormone (hGH) secretion and turnover in three patients with Laron-type dwarfism. 62 57
3356536 1988
40
Absence of serum growth hormone binding protein in patients with growth hormone receptor deficiency (Laron dwarfism). 62 57
3474620 1987
41
Tissues of the Laron dwarf are sensitive to insulin-like growth factor I but not to growth hormone. 62 57
3031118 1987
42
Defect of human growth hormone receptors in the liver of two patients with Laron-type dwarfism. 62 57
6321400 1984
43
Peripheral unresponsiveness to human growth hormone in Laron dwarfism. 62 57
6106895 1980
44
Puberty in Laron type dwarfism. 62 57
7408914 1980
45
Receptor-active growth hormone in Laron dwarfism. 62 57
177445 1976
46
A novel C-terminal growth hormone receptor (GHR) mutation results in impaired GHR-STAT5 but normal STAT-3 signaling. 5
15536163 2005
47
Leptin concentrations in GH deficiency: the effect of GH insensitivity. 5
11836282 2002
48
Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity. 5
11468686 2001
49
Stature in Ecuadorians heterozygous for growth hormone receptor gene E180 splice mutation does not differ from that of homozygous normal relatives. 5
9661611 1998
50
Aspartate 171 is the major primate-specific determinant of human growth hormone. Engineering porcine growth hormone to activate the human receptor. 57
9341147 1997

Variations for Laron Syndrome

ClinVar genetic disease variations for Laron Syndrome:

5 (show top 50) (show all 123)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GHR NM_000163.5(GHR):c.504T>G (p.His168Gln) SNV Pathogenic
8663 rs121909373 GRCh37: 5:42699990-42699990
GRCh38: 5:42699888-42699888
2 GHR NM_000163.5(GHR):c.335G>C (p.Cys112Ser) SNV Pathogenic
8662 rs121909372 GRCh37: 5:42695087-42695087
GRCh38: 5:42694985-42694985
3 GHR NM_000163.5(GHR):c.102G>A (p.Trp34Ter) SNV Pathogenic
8657 rs121909370 GRCh37: 5:42629171-42629171
GRCh38: 5:42629069-42629069
4 GHR NM_000163.5(GHR):c.618+792A>G SNV Pathogenic
8655 GRCh37: 5:42700896-42700896
GRCh38: 5:42700794-42700794
5 GHR NM_000163.5(GHR):c.512T>C (p.Ile171Thr) SNV Pathogenic
8654 rs121909367 GRCh37: 5:42699998-42699998
GRCh38: 5:42699896-42699896
6 GHR NM_000163.5(GHR):c.518T>G (p.Val173Gly) SNV Pathogenic
8648 rs121909369 GRCh37: 5:42700004-42700004
GRCh38: 5:42699902-42699902
7 GHR NM_000163.5(GHR):c.515A>C (p.Gln172Pro) SNV Pathogenic
8645 rs121909368 GRCh37: 5:42700001-42700001
GRCh38: 5:42699899-42699899
8 GHR NM_000163.5(GHR):c.619-1G>T SNV Pathogenic
8642 rs730880281 GRCh37: 5:42711308-42711308
GRCh38: 5:42711206-42711206
9 GHR NM_000163.5(GHR):c.266+1G>A SNV Pathogenic
8640 GRCh37: 5:42689122-42689122
GRCh38: 5:42689020-42689020
10 GHR NM_000163.5(GHR):c.703C>T (p.Arg235Ter) SNV Pathogenic
8639 rs121909363 GRCh37: 5:42711393-42711393
GRCh38: 5:42711291-42711291
11 GHR NM_000163.5(GHR):c.594A>G (p.Glu198=) SNV Pathogenic
8635 rs121909360 GRCh37: 5:42700080-42700080
GRCh38: 5:42699978-42699978
12 GHR NM_000163.5(GHR):c.168C>A (p.Cys56Ter) SNV Pathogenic
8634 rs121909359 GRCh37: 5:42689023-42689023
GRCh38: 5:42688921-42688921
13 GHR NM_000163.5(GHR):c.181C>T (p.Arg61Ter) SNV Pathogenic
8633 rs121909358 GRCh37: 5:42689036-42689036
GRCh38: 5:42688934-42688934
14 GHR NM_000163.5(GHR):c.341T>C (p.Phe114Ser) SNV Pathogenic
8632 rs121909357 GRCh37: 5:42695093-42695093
GRCh38: 5:42694991-42694991
15 GHR GHR, EX4,6DEL DEL Pathogenic
8631 GRCh37:
GRCh38:
16 GHR NM_000163.5(GHR):c.281G>A (p.Trp94Ter) SNV Pathogenic
397577 rs1060499692 GRCh37: 5:42695033-42695033
GRCh38: 5:42694931-42694931
17 GHR NM_000163.5(GHR):c.945G>A (p.Lys315=) SNV Pathogenic
492774 rs1554040858 GRCh37: 5:42718223-42718223
GRCh38: 5:42718121-42718121
18 GHR NM_000163.5(GHR):c.364T>C (p.Trp122Arg) SNV Pathogenic
492773 rs190314158 GRCh37: 5:42695116-42695116
GRCh38: 5:42695014-42695014
19 GHR NM_000163.5(GHR):c.303C>A (p.Cys101Ter) SNV Pathogenic
8659 rs121909371 GRCh37: 5:42695055-42695055
GRCh38: 5:42694953-42694953
20 GHR NM_000163.5(GHR):c.192_193del (p.Ser65fs) DEL Pathogenic
1206352 GRCh37: 5:42689044-42689045
GRCh38: 5:42688942-42688943
21 GHR NM_000163.5(GHR):c.743_744del (p.Tyr248fs) DEL Pathogenic
8643 GRCh37: 5:42711432-42711433
GRCh38: 5:42711330-42711331
22 GHR NP_000154.1:p.Ala442Serfs*27 DEL Pathogenic
8656 GRCh37:
GRCh38:
23 GHR NM_000163.5(GHR):c.1734del (p.Arg578fs) DEL Pathogenic
8660 GRCh37: 5:42719342-42719342
GRCh38: 5:42719240-42719240
24 GHR NM_000163.5(GHR):c.267-2A>G SNV Pathogenic
869191 rs1757597156 GRCh37: 5:42695017-42695017
GRCh38: 5:42694915-42694915
25 GHR NM_000163.5(GHR):c.70+5G>A SNV Likely Pathogenic
1332694 GRCh37: 5:42566051-42566051
GRCh38: 5:42565949-42565949
26 GHR NM_000163.5(GHR):c.344A>C (p.Asn115Thr) SNV Likely Pathogenic
807419 rs1579626395 GRCh37: 5:42695096-42695096
GRCh38: 5:42694994-42694994
27 GHR NM_000163.5(GHR):c.508G>C (p.Asp170His) SNV Likely Pathogenic
8653 rs121909366 GRCh37: 5:42699994-42699994
GRCh38: 5:42699892-42699892
28 GHR NM_000163.5(GHR):c.484G>A (p.Val162Ile) SNV Conflicting Interpretations Of Pathogenicity
8652 rs6413484 GRCh37: 5:42699970-42699970
GRCh38: 5:42699868-42699868
29 GHR NM_000163.5(GHR):c.1146C>T (p.Gly382=) SNV Uncertain Significance
717474 rs533441671 GRCh37: 5:42718755-42718755
GRCh38: 5:42718653-42718653
30 GHR NM_000163.5(GHR):c.273T>A (p.Thr91=) SNV Uncertain Significance
353680 rs138491809 GRCh37: 5:42695025-42695025
GRCh38: 5:42694923-42694923
31 GHR NM_000163.5(GHR):c.12G>C (p.Trp4Cys) SNV Uncertain Significance
492772 rs1554020272 GRCh37: 5:42565988-42565988
GRCh38: 5:42565886-42565886
32 GHR NM_000163.5(GHR):c.*2376A>G SNV Uncertain Significance
906818 rs181681602 GRCh37: 5:42721902-42721902
GRCh38: 5:42721800-42721800
33 LOC107963950, GHR NM_000163.5(GHR):c.-176A>G SNV Uncertain Significance
907633 rs1314535276 GRCh37: 5:42423893-42423893
GRCh38: 5:42423791-42423791
34 GHR NM_000163.5(GHR):c.724G>A (p.Glu242Lys) SNV Uncertain Significance
907708 rs121909364 GRCh37: 5:42711414-42711414
GRCh38: 5:42711312-42711312
35 GHR NM_000163.5(GHR):c.743A>G (p.Tyr248Cys) SNV Uncertain Significance
907709 rs557134454 GRCh37: 5:42711433-42711433
GRCh38: 5:42711331-42711331
36 GHR NM_000163.5(GHR):c.*724G>T SNV Uncertain Significance
907759 rs1579681863 GRCh37: 5:42720250-42720250
GRCh38: 5:42720148-42720148
37 GHR NM_000163.5(GHR):c.*832G>A SNV Uncertain Significance
907760 rs1006780293 GRCh37: 5:42720358-42720358
GRCh38: 5:42720256-42720256
38 GHR NM_000163.5(GHR):c.723C>T (p.Gly241_Glu242=) SNV Uncertain Significance
1705333 GRCh37: 5:42711413-42711413
GRCh38: 5:42711311-42711311
39 GHR NM_000163.5(GHR):c.535C>T (p.Arg179Cys) SNV Uncertain Significance
Uncertain Significance
Likely Benign
8637 rs121909362 GRCh37: 5:42700021-42700021
GRCh38: 5:42699919-42699919
40 GHR NM_000163.5(GHR):c.875+10G>C SNV Uncertain Significance
353682 rs35111599 GRCh37: 5:42713631-42713631
GRCh38: 5:42713529-42713529
41 GHR NM_000163.5(GHR):c.*981G>A SNV Uncertain Significance
353704 rs886060645 GRCh37: 5:42720507-42720507
GRCh38: 5:42720405-42720405
42 GHR NM_000163.5(GHR):c.876-15T>G SNV Uncertain Significance
353683 rs199960137 GRCh37: 5:42718139-42718139
GRCh38: 5:42718037-42718037
43 GHR NM_000163.5(GHR):c.82A>G (p.Ile28Val) SNV Uncertain Significance
737265 rs143287692 GRCh37: 5:42629151-42629151
GRCh38: 5:42629049-42629049
44 GHR NM_000163.5(GHR):c.99C>G (p.Pro33=) SNV Uncertain Significance
594102 rs76183160 GRCh37: 5:42629168-42629168
GRCh38: 5:42629066-42629066
45 GHR NM_000163.5(GHR):c.267-3T>C SNV Uncertain Significance
905101 rs201917287 GRCh37: 5:42695016-42695016
GRCh38: 5:42694914-42694914
46 GHR NM_000163.5(GHR):c.486C>T (p.Val162=) SNV Uncertain Significance
906682 rs773964952 GRCh37: 5:42699972-42699972
GRCh38: 5:42699870-42699870
47 GHR NM_000163.5(GHR):c.686G>A (p.Arg229His) SNV Uncertain Significance
281656 rs6177 GRCh37: 5:42711376-42711376
GRCh38: 5:42711274-42711274
48 GHR NM_000163.5(GHR):c.814A>G (p.Ile272Val) SNV Uncertain Significance
907710 rs35040971 GRCh37: 5:42713560-42713560
GRCh38: 5:42713458-42713458
49 GHR NM_000163.5(GHR):c.1002C>T (p.Pro334=) SNV Uncertain Significance
907711 rs148387362 GRCh37: 5:42718611-42718611
GRCh38: 5:42718509-42718509
50 GHR NM_000163.5(GHR):c.*1539G>A SNV Uncertain Significance
353707 rs181187685 GRCh37: 5:42721065-42721065
GRCh38: 5:42720963-42720963

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

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 GHR p.Arg89Lys VAR_002709
2 GHR p.Phe114Ser VAR_002710 rs121909357
3 GHR p.Val143Ala VAR_002711
4 GHR p.Val162Asp VAR_002712
5 GHR p.Asp170His VAR_002713 rs121909366
6 GHR p.Arg179Cys VAR_002714 rs121909362
7 GHR p.Arg229Gly VAR_002715
8 GHR p.Cys56Ser VAR_018426
9 GHR p.Ser58Leu VAR_018427
10 GHR p.Trp68Arg VAR_018428
11 GHR p.Pro149Gln VAR_018429 rs121909365
12 GHR p.Ile171Thr VAR_018431 rs121909367
13 GHR p.Gln172Pro VAR_018432 rs121909368
14 GHR p.Val173Gly VAR_018433 rs121909369
15 GHR p.Tyr226Cys VAR_018434
16 GHR p.Ser244Ile VAR_018435 rs1164396446
17 GHR p.Asp262Asn VAR_018436

Expression for Laron Syndrome

Search GEO for disease gene expression data for Laron Syndrome.

Pathways for Laron Syndrome

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

(show all 16)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.31 STAT5B STAT1 IL18R1 IGF2 IGF1 GHR
2
Show member pathways
13.16 STAT5B STAT1 IL18R1 IGF2 IGF1 GH1
3
Show member pathways
12.48 GH1 GHR IGF1 IGFBP3 STAT1
4
Show member pathways
12.38 STAT5B STAT1 IGF2 IGF1 GH1
5 12.25 SIRT1 IGFBP3 IGFBP2 IGFBP1 ADIPOQ
6
Show member pathways
11.99 IGFBP3 IGFBP2 IGFBP1 IGF2 IGF1
7
Show member pathways
11.8 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
8 11.77 STAT5B STAT1 IGF1 GH1 ADIPOQ
9
Show member pathways
11.69 STAT5B STAT1 IL18R1
10 11.65 IGFBP3 IGF1 ADIPOQ
11
Show member pathways
11.2 STAT5B STAT1 IGF2 IGF1 GHR GH1
12 11.15 IGFBP3 IGFBP2 IGFBP1
13
Show member pathways
11.05 STAT5B STAT1 GHR GH1
14 10.96 STAT5B STAT1
15 10.95 STAT5B IL18R1
16 10.41 SIRT1 IGF1

GO Terms for Laron Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 10.32 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2 IGF1
2 extracellular space GO:0005615 9.98 MIR132 IGFBP3 IGFBP2 IGFBP1 IGFALS IGF2
3 insulin-like growth factor binding protein complex GO:0016942 9.56 IGFBP3 IGF1
4 growth hormone receptor complex GO:0070195 9.46 GH1 GHR
5 insulin-like growth factor ternary complex GO:0042567 9.1 IGFBP3 IGFALS IGF1

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

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.4 ADIPOQ GH1 GHRHR IGF1 IGFALS IGFBP1
2 positive regulation of cell population proliferation GO:0008284 10.17 GHRHR IGF1 IGF2 MIR132 SIRT1 STAT1
3 cellular response to insulin stimulus GO:0032869 10.13 ADIPOQ GHR GHRHR STAT1
4 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 10.08 IGF1 GHR GH1
5 response to nutrient GO:0007584 10.08 STAT1 IGFBP2 ADIPOQ
6 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043124 10.06 STAT1 SIRT1 ADIPOQ
7 response to insulin GO:0032868 10.02 SIRT1 IGFBP2 GHRHR
8 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 10.02 IGF2 IGF1 GHR GH1 ADIPOQ
9 negative regulation of tumor necrosis factor production GO:0032720 10.01 MIR132 IGF1 ADIPOQ
10 cellular response to hormone stimulus GO:0032870 10.01 STAT5B IGFBP2 GHR
11 response to glucocorticoid GO:0051384 10.01 IGFBP2 GHRHR GHR ADIPOQ
12 response to peptide hormone GO:0043434 9.99 STAT5B STAT1 GHR
13 regulation of multicellular organism growth GO:0040014 9.99 STAT5B IGF1 GHR
14 receptor signaling pathway via JAK-STAT GO:0007259 9.97 GH1 GHR STAT1 STAT5B
15 regulation of glucose metabolic process GO:0010906 9.95 SIRT1 IGFBP3 ADIPOQ
16 growth hormone receptor signaling pathway GO:0060396 9.92 GHR GH1
17 positive regulation of cAMP-dependent protein kinase activity GO:2000481 9.88 ADIPOQ SIRT1
18 positive regulation of glycogen (starch) synthase activity GO:2000467 9.87 IGF2 ADIPOQ
19 taurine metabolic process GO:0019530 9.86 STAT5B GHR
20 positive regulation of activated T cell proliferation GO:0042104 9.86 STAT5B IGFBP2 IGF2 IGF1
21 insulin-like growth factor receptor signaling pathway GO:0048009 9.85 IGF2 IGF1 GHR
22 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.76 GH1 GHRHR IGF1 IGFBP3
23 negative regulation of prostaglandin biosynthetic process GO:0031393 9.72 SIRT1 MIR132
24 positive regulation of multicellular organism growth GO:0040018 9.65 STAT5B IGF2 GHRHR GHR GH1
25 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.17 IGFBP3 IGFBP2 IGFBP1 GHRHR

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

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 9.92 IGF2 IGF1 GH1 ADIPOQ
2 insulin-like growth factor I binding GO:0031994 9.73 IGFBP3 IGFBP2 IGFBP1
3 insulin-like growth factor II binding GO:0031995 9.63 IGFBP3 IGFBP2 IGFBP1
4 growth factor binding GO:0019838 9.5 IGFBP3 IGFBP2 IGFBP1 GHRHR GHR
5 insulin-like growth factor binding GO:0005520 9.17 IGFBP3 IGFBP2 IGFBP1 IGFALS

Sources for Laron Syndrome

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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