IGHD2
MCID: ISL114
MIFTS: 40

Isolated Growth Hormone Deficiency, Type Ii (IGHD2)

Categories: Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Isolated Growth Hormone Deficiency, Type Ii

MalaCards integrated aliases for Isolated Growth Hormone Deficiency, Type Ii:

Name: Isolated Growth Hormone Deficiency, Type Ii 56 71
Isolated Growth Hormone Deficiency Type Ii 12 52 58 73 15
Ighd Ii 56 12 52 73 54
Growth Hormone Deficiency, Isolated, Type Ii 56 13 39
Ighd2 56 52 73
Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency Autosomal Dominant 52 73
Congenital Isolated Growth Hormone Deficiency Type Ii 12 58
Congenital Isolated Gh Deficiency Type Ii 12 58
Congenital Ighd Type Ii 12 58
Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency, Autosomal Dominant 56
Autosomal Dominant Pituitary Dwarfism Due to Isolated Growth Hormone Deficiency 12
Growth Hormone Deficiency, Isolated, Autosomal Dominant 56
Growth Hormone Deficiency, Isolated Autosomal Dominant 52
Autosomal Dominant Isolated Growth Hormone Deficiency 12
Growth Hormone Deficiency Isolated Autosomal Dominant 73
Isolated Growth Hormone Deficiency Type 2 52
Growth Hormone Deficiency, Isolated, 2 73

Characteristics:

Orphanet epidemiological data:

58
isolated growth hormone deficiency type ii
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant form


HPO:

31
isolated growth hormone deficiency, type ii:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0060872
OMIM 56 173100
OMIM Phenotypic Series 56 PS262400
MeSH 43 D004393
ICD10 32 E23.0
ICD10 via Orphanet 33 E23.0
UMLS via Orphanet 72 C0271567
Orphanet 58 ORPHA231679
MedGen 41 C0271567
UMLS 71 C0271567

Summaries for Isolated Growth Hormone Deficiency, Type Ii

OMIM : 56 Type II IGHD is an autosomal dominant disorder characterized by low but detectable levels of growth hormone (GH), variable height deficit and age at presentation, and good response to rhGH. Patients may show anterior pituitary hypoplasia on MRI (summary by Phillips and Cogan, 1994; Alatzoglou and Dattani, 2012). (173100)

MalaCards based summary : Isolated Growth Hormone Deficiency, Type Ii, also known as isolated growth hormone deficiency type ii, is related to isolated growth hormone deficiency and growth hormone deficiency. An important gene associated with Isolated Growth Hormone Deficiency, Type Ii is GH1 (Growth Hormone 1), and among its related pathways/superpathways is Relaxin signaling pathway. Affiliated tissues include pituitary, and related phenotypes are severe short stature and growth hormone deficiency

Disease Ontology : 12 An isolated growth hormone deficiency characterized by autosomal dominant inheritance of low but detectable levels of GH1 resulting in variable degrees of dwarfism which are responsive to growth hormone therapy that has material basis in dominant negative mutations in the GH1 gene on chromosome 17q23.3.

UniProtKB/Swiss-Prot : 73 Growth hormone deficiency, isolated, 2: An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy.

Related Diseases for Isolated Growth Hormone Deficiency, Type Ii

Diseases related to Isolated Growth Hormone Deficiency, Type Ii via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 59)
# Related Disease Score Top Affiliating Genes
1 isolated growth hormone deficiency 30.9 PROP1 POU1F1 IGF1 HESX1 GHRHR GHRH
2 growth hormone deficiency 30.7 HESX1 GHRHR GH1
3 pituitary hypoplasia 29.9 POU1F1 HESX1 GHRHR GH1
4 central precocious puberty 10.3 IGF1 GH1
5 hypothyroidism, central, with testicular enlargement 10.3 PROP1 POU1F1
6 marasmus 10.3 IGF1 GH1
7 traumatic brain injury 10.2 IGF1 GH1
8 hypothyroidism, congenital, nongoitrous, 4 10.2 PROP1 POU1F1 GH1
9 isolated growth hormone deficiency, type ia 10.2
10 acth deficiency, isolated 10.2 PROP1 POU1F1
11 pituitary apoplexy 10.2 IGF1 GH1
12 laron syndrome 10.2 IGF1 GHRHR GH1
13 empty sella syndrome 10.1 PROP1 IGF1 GH1
14 intracranial hypertension, idiopathic 10.1 IGF1 GH1
15 congenital hypothyroidism 10.1 POU1F1 IGF1 GH1
16 pituitary hormone deficiency, combined, 1 10.1 POU1F1 HESX1
17 acid-labile subunit deficiency 10.0
18 pituitary adenoma, prolactin-secreting 10.0 POU1F1 IGF1 GHRHR GH1
19 mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes 10.0 GHRH GH1
20 pituitary tumors 10.0 PROP1 POU1F1 IGF1 GH1
21 craniopharyngioma 10.0 PROP1 POU1F1 IGF1 GH1
22 gigantism 9.9 GHRH GH1
23 hypothyroidism due to deficient transcription factors involved in pituitary development or function 9.9 PROP1 POU1F1 HESX1
24 combined pituitary hormone deficiencies, genetic forms 9.9 PROP1 POU1F1 HESX1
25 combined pituitary hormone deficiency 9.9 PROP1 POU1F1 HESX1
26 borjeson-forssman-lehmann syndrome 9.9 PROP1 POU1F1 HESX1
27 hypothalamic obesity 9.9 IGF1 GHRH
28 pituitary-dependent cushing's disease 9.9 GHRH GH1
29 pituitary infarct 9.9 IGF1 GHRH
30 carcinoid syndrome 9.8 IGF1 GHRH
31 pituitary adenoma 1, multiple types 9.8 IGF1 GH1
32 hormone producing pituitary cancer 9.8 IGF1 GHRH
33 isolated growth hormone deficiency, type ib 9.8 GHRHR GHRH GH1
34 pituitary stalk interruption syndrome 9.8 POU1F1 HESX1 GHRHR GH1
35 dwarfism 9.8 GHRHR GHRH GH1
36 hypothalamic disease 9.8 IGF1 GHRH GH1
37 hyperpituitarism 9.7 IGF1 GHRH GH1
38 pseudohypoparathyroidism, type ia 9.7 IGF1 GHRH GH1
39 functioning pituitary adenoma 9.7 IGF1 GHRH GH1
40 growth hormone secreting pituitary adenoma 9.7 IGF1 GHRHR GHRH
41 fibrous dysplasia 9.7 IGF1 GHRH GH1
42 islet cell tumor 9.7 IGF1 GHRH GH1
43 hyperprolactinemia 9.7 IGF1 GHRH GH1
44 insulin-like growth factor i 9.7 IGF1 GHRH GH1
45 turner syndrome 9.7 IGF1 GHRH GH1
46 cryptorchidism, unilateral or bilateral 9.7 PROP1 IGF1 HESX1
47 nerve compression syndrome 9.7 IGF1 GHRH
48 vipoma 9.6 GHRH GH1
49 anorexia nervosa 9.6 IGF1 GHRH GH1
50 acromegaly 9.5 IGF1 GHRHR GHRH GH1

Graphical network of the top 20 diseases related to Isolated Growth Hormone Deficiency, Type Ii:



Diseases related to Isolated Growth Hormone Deficiency, Type Ii

Symptoms & Phenotypes for Isolated Growth Hormone Deficiency, Type Ii

Human phenotypes related to Isolated Growth Hormone Deficiency, Type Ii:

31
# Description HPO Frequency HPO Source Accession
1 severe short stature 31 HP:0003510
2 growth hormone deficiency 31 HP:0000824
3 pituitary dwarfism 31 HP:0000839

Symptoms via clinical synopsis from OMIM:

56
Growth:
dwarfism

Lab:
insulin responses to glucose and to arginine usually greater than normal
no insulinopenia

Endocrine:
isolated growth hormone deficiency

Clinical features from OMIM:

173100

MGI Mouse Phenotypes related to Isolated Growth Hormone Deficiency, Type Ii:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.36 CREB3L2 ELF3 GHRH GHRHR HESX1 IGF1

Drugs & Therapeutics for Isolated Growth Hormone Deficiency, Type Ii

Search Clinical Trials , NIH Clinical Center for Isolated Growth Hormone Deficiency, Type Ii

Genetic Tests for Isolated Growth Hormone Deficiency, Type Ii

Anatomical Context for Isolated Growth Hormone Deficiency, Type Ii

MalaCards organs/tissues related to Isolated Growth Hormone Deficiency, Type Ii:

40
Pituitary

Publications for Isolated Growth Hormone Deficiency, Type Ii

Articles related to Isolated Growth Hormone Deficiency, Type Ii:

(show top 50) (show all 54)
# Title Authors PMID Year
1
Isolated growth hormone deficiency type II caused by a point mutation that alters both splice site strength and splicing enhancer function. 54 61 6 56
18554279 2008
2
A novel IVS2 -2A>T splicing mutation in the GH-1 gene in familial isolated growth hormone deficiency type II in the spectrum of other splicing mutations in the Russian population. 6 54 61
12574219 2003
3
An exonic mutation of the GH-1 gene causing familial isolated growth hormone deficiency type II. 6 54 61
12000366 2002
4
Variable phenotypes in familial isolated growth hormone deficiency caused by a G6664A mutation in the GH-1 gene. 54 6
17785368 2007
5
Exon splice enhancer mutation (GH-E32A) causes autosomal dominant growth hormone deficiency. 54 6
17726075 2007
6
A novel deletion in the GH1 gene including the IVS3 branch site responsible for autosomal dominant isolated growth hormone deficiency. 54 6
16368751 2006
7
An exon splice enhancer mutation causes autosomal dominant GH deficiency. 54 6
11836331 2002
8
A recurring dominant negative mutation causes autosomal dominant growth hormone deficiency--a clinical research center study. 6 54
8530604 1995
9
Phenotype-genotype correlations in congenital isolated growth hormone deficiency (IGHD). 56
22139958 2012
10
Genetic screening of a Dutch population with isolated GH deficiency (IGHD). 6
18785993 2009
11
Isolated autosomal dominant growth hormone deficiency: an evolving pituitary deficit? A multicenter follow-up study. 56
15671105 2005
12
Mutations in intron 3 of GH-1 gene associated with isolated GH deficiency type II in three Japanese families. 6
10469016 1999
13
A Japanese family with autosomal dominant growth hormone deficiency. 6
10445339 1999
14
Inhibition of growth hormone (GH) secretion by a mutant GH-I gene product in neuroendocrine cells containing secretory granules: an implication for isolated GH deficiency inherited in an autosomal dominant manner. 6
10372722 1999
15
Familial growth hormone deficiency associated with MRI abnormalities. 56
9805128 1998
16
Characterization of an intron splice enhancer that regulates alternative splicing of human GH pre-mRNA. 6
9700205 1998
17
De novo mutations of the growth hormone gene: an important cause of congenital isolated growth hormone deficiency? 6
9578959 1998
18
Genetic defects in the control of growth hormone secretion. 6
9554464 1998
19
A novel mechanism of aberrant pre-mRNA splicing in humans. 6
9175738 1997
20
Mechanisms responsible for dominant expression of human growth hormone gene mutations. 6
8923859 1996
21
An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA. 6
7567462 1995
22
18p monosomy with GH-deficiency and empty sella: good response to GH-treatment. 56
7554351 1995
23
Screening for growth hormone (GH) gene splice-site mutations in sporadic cases with severe isolated GH deficiency using ectopic transcript analysis. 6
7714096 1995
24
Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency. 56
8288694 1994
25
18p- syndrome and hypopituitarism. 56
1404301 1992
26
A family case with autosomal-dominantly inherited pituitary dwarfism. 56
3660403 1987
27
Familial isolated growth hormone deficiency. 56
7307312 1981
28
Aetiology of idiopathic growth hormone deficiency in England and Wales. 56
848998 1977
29
Autosomal dominant transmission of isolated growth hormone deficiency in iris-dental dysplasia (Rieger's syndrome). 56
4214375 1974
30
Isolated growth hormone deficiency. Two families with autosomal dominant inheritance. 56
4361890 1974
31
Studies in high-deficient dwarfs: the type II anomaly. 56
5050736 1972
32
Hereditary isolated somatotropin deficiency: effects of human growth hormone administration. 56
5010465 1972
33
[Familial hypopituitarism]. 56
5511839 1970
34
A metabolic and hormonal basis for classifying ateliotic dwarfs. 56
4180815 1969
35
Growth-hormone deficiency in man: an isolated, recessively inherited defect. 56
4287048 1966
36
Intrauterine growth retardation. 56
13783175 1961
37
Rescue of pituitary function in a mouse model of isolated growth hormone deficiency type II by RNA interference. 54 61
18006625 2008
38
Mutant and misfolded human growth hormone is rapidly degraded through the proteasomal degradation pathway in a cellular model for isolated growth hormone deficiency type II. 61 54
17927666 2007
39
GH-1 gene splicing mutations: molecular basis of hereditary isolated growth hormone deficiency in children. 61 54
17073157 2006
40
Disruption of exon definition produces a dominant-negative growth hormone isoform that causes somatotroph death and IGHD II. 61 54
12720086 2003
41
Decreased Activity of the Ghrhr and Gh Promoters Causes Dominantly Inherited GH Deficiency in Humanized GH1 Mouse Models. 61
31436800 2019
42
Endoplasmic Reticulum (ER) Stress and Endocrine Disorders. 61
28208663 2017
43
Targeting GH-1 splicing as a novel pharmacological strategy for growth hormone deficiency type II. 61
27457999 2017
44
Splice site mutations in GH1 detected in previously (Genetically) undiagnosed families with congenital isolated growth hormone deficiency type II. 61
24280736 2013
45
A novel GH1 mutation in a family with isolated growth hormone deficiency type II. 61
22188748 2012
46
Pharmacologic correction of dominant-negative GH1 deficiency causing mutations. 61
21707947 2011
47
Growth hormone (GH)-releasing hormone increases the expression of the dominant-negative GH isoform in cases of isolated GH deficiency due to GH splice-site mutations. 54
20351314 2010
48
Growth hormone (GH) deficiency type II: a novel GH-1 gene mutation (GH-R178H) affecting secretion and action. 54
19952226 2010
49
A molecular basis for variation in clinical severity of isolated growth hormone deficiency type II. 61
19837935 2009
50
Growth hormone deficiency and splicing fidelity: two serine/arginine-rich proteins, ASF/SF2 and SC35, act antagonistically. 61
18586677 2008

Variations for Isolated Growth Hormone Deficiency, Type Ii

ClinVar genetic disease variations for Isolated Growth Hormone Deficiency, Type Ii:

6 (show all 16) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GH1 NM_000515.5(GH1):c.291+6T>CSNV Pathogenic 15968 rs797044450 17:61995371-61995371 17:63918011-63918011
2 GH1 NM_000515.5(GH1):c.291+1G>ASNV Pathogenic 15970 rs71640277 17:61995376-61995376 17:63918016-63918016
3 GH1 NM_000515.5(GH1):c.291+1G>CSNV Pathogenic 15971 rs71640277 17:61995376-61995376 17:63918016-63918016
4 GH1 NM_000515.5(GH1):c.291+28G>ASNV Pathogenic 15972 rs863223306 17:61995349-61995349 17:63917989-63917989
5 GH1 GH1, IVS3DS, 18-BP DEL, +28-45deletion Pathogenic 15973
6 GH1 NM_000515.5(GH1):c.291+5G>ASNV Pathogenic 15975 rs863223307 17:61995372-61995372 17:63918012-63918012
7 GH1 GH1, EX3, A-G, +5SNV Pathogenic 15977
8 GH1 GH1, EX3DELdeletion Pathogenic 15978
9 GH1 NM_000515.5(GH1):c.172-2A>TSNV Pathogenic 15979 rs863223309 17:61995498-61995498 17:63918138-63918138
10 GH1 NM_000515.5(GH1):c.291+2T>CSNV Pathogenic 15980 rs863223310 17:61995375-61995375 17:63918015-63918015
11 GH1 GH1, IVS3, 22-BP DELdeletion Pathogenic 15982
12 GH1 NM_000515.5(GH1):c.626G>A (p.Arg209His)SNV Pathogenic 15983 rs137853223 17:61994697-61994697 17:63917337-63917337
13 GH1 GH1, EX3, A-C, +2SNV Pathogenic 15984
14 GH1 GH1, EX3, G-A, +1SNV Pathogenic 15985
15 GH1 NM_000515.5(GH1):c.-4T>GSNV Benign/Likely benign 324460 rs6173 17:61996140-61996140 17:63918780-63918780
16 GH1 NM_000515.5(GH1):c.7A>G (p.Thr3Ala)SNV Benign 289503 rs2001345 17:61996130-61996130 17:63918770-63918770

UniProtKB/Swiss-Prot genetic disease variations for Isolated Growth Hormone Deficiency, Type Ii:

73
# Symbol AA change Variation ID SNP ID
1 GH1 p.Arg209His VAR_015815 rs137853223

Expression for Isolated Growth Hormone Deficiency, Type Ii

Search GEO for disease gene expression data for Isolated Growth Hormone Deficiency, Type Ii.

Pathways for Isolated Growth Hormone Deficiency, Type Ii

Pathways related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.7 POU1F1 IGF1 GHRHR GHRH GH1 CREB3L2

GO Terms for Isolated Growth Hormone Deficiency, Type Ii

Cellular components related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 9.1 PROP1 POU1F1 HESX1 ELF5 ELF3 CREB3L2

Biological processes related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.99 PROP1 POU1F1 HESX1 ELF5 ELF3 CREB3L2
2 positive regulation of transcription by RNA polymerase II GO:0045944 9.95 PROP1 POU1F1 IGF1 ELF5 ELF3 CREB3L2
3 pituitary gland development GO:0021983 9.5 PROP1 POU1F1 HESX1
4 determination of adult lifespan GO:0008340 9.49 POU1F1 GHRHR
5 positive regulation of growth hormone secretion GO:0060124 9.46 GHRHR GHRH
6 positive regulation of multicellular organism growth GO:0040018 9.46 POU1F1 GHRHR GHRH GH1
7 positive regulation of hormone secretion GO:0046887 9.43 GHRHR GHRH
8 regulation of insulin-like growth factor receptor signaling pathway GO:0043567 9.4 POU1F1 GHRHR
9 somatotropin secreting cell differentiation GO:0060126 9.37 PROP1 POU1F1
10 somatotropin secreting cell development GO:0060133 9.26 POU1F1 GHRHR
11 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 9.26 IGF1 GHRHR GHRH GH1
12 adenohypophysis development GO:0021984 8.92 PROP1 POU1F1 GHRHR GHRH

Molecular functions related to Isolated Growth Hormone Deficiency, Type Ii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.56 POU1F1 HESX1 ELF3 CREB3L2
2 sequence-specific DNA binding GO:0043565 9.55 PROP1 POU1F1 HESX1 ELF5 ELF3
3 protein C-terminus binding GO:0008022 9.5 RAB3A PROP1 HESX1
4 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.43 PROP1 POU1F1 HESX1 ELF5 ELF3 CREB3L2
5 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.02 PROP1 POU1F1 ELF5 ELF3 CREB3L2

Sources for Isolated Growth Hormone Deficiency, Type Ii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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