IGHD4
MCID: ISL123
MIFTS: 34

Isolated Growth Hormone Deficiency, Type Iv (IGHD4)

Categories: Endocrine diseases, Genetic diseases

Aliases & Classifications for Isolated Growth Hormone Deficiency, Type Iv

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

Name: Isolated Growth Hormone Deficiency, Type Iv 57 72
Dwarfism of Sindh 57 72 6
Growth Hormone Deficiency, Isolated, Type Iv 57 72
Isolated Growth Hormone Deficiency, Type 4 29 6
Ighd4 57 72
Isolated Growth Hormone Deficiency, Type Ib, Formerly; Ighd1b, Formerly 57
Isolated Growth Hormone Deficiency, Type Ib, Formerly 57
Growth Hormone Deficiency, Isolated, 4 72
Ighd1b, Formerly 57

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
isolated growth hormone deficiency, type iv:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM® 57 618157
OMIM Phenotypic Series 57 PS262400
MeSH 44 D004393

Summaries for Isolated Growth Hormone Deficiency, Type Iv

OMIM® : 57 IGHD type IV is an autosomal recessive disorder characterized by early and severe growth failure (height SDS up to -7.4), a blunted growth hormone (GH) response to different provocation tests and low insulin-like growth factor-I (IGF1; 147440) and IGF-binding protein-3 (IGFBP3; 146732) concentrations, and a good response to growth hormone treatment (summary by Alatzoglou et al., 2014). For general phenotypic information and a discussion of genetic heterogeneity of IGHD, see 262400. (618157) (Updated 20-May-2021)

MalaCards based summary : Isolated Growth Hormone Deficiency, Type Iv, also known as dwarfism of sindh, is related to isolated growth hormone deficiency, type ib and dwarfism. An important gene associated with Isolated Growth Hormone Deficiency, Type Iv is GHRHR (Growth Hormone Releasing Hormone Receptor), and among its related pathways/superpathways is G-Beta Gamma Signaling. The drug Hormones has been mentioned in the context of this disorder. Affiliated tissues include pituitary and bone, and related phenotypes are severe short stature and delayed skeletal maturation

UniProtKB/Swiss-Prot : 72 Growth hormone deficiency, isolated, 4: An autosomal recessive deficiency of growth hormone leading to early and severe growth failure and short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy.

Related Diseases for Isolated Growth Hormone Deficiency, Type Iv

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



Diseases related to Isolated Growth Hormone Deficiency, Type Iv

Symptoms & Phenotypes for Isolated Growth Hormone Deficiency, Type Iv

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

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 severe short stature 31 very rare (1%) HP:0003510
2 delayed skeletal maturation 31 HP:0002750
3 anterior pituitary hypoplasia 31 HP:0010627
4 decreased serum insulin-like growth factor 1 31 HP:0030353
5 decreased response to growth hormone stimuation test 31 HP:0000824
6 impaired growth-hormone response to insulin stimulation test 31 HP:0031079

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Face:
frontal bossing

Abdomen External Features:
truncal obesity

Growth Height:
proportionate short stature

Voice:
high-pitched voice

Growth Weight:
truncal obesity

Endocrine Features:
growth hormone deficiency
growth hormone releasing hormone resistance
flat growth hormone response to clonidine or insulin-induced hypoglycemia
flat growth hormone response to ghrh (primed and non-primed)
low serum igf-1
more
Skeletal:
delayed bone age

Growth Other:
severe growth failure (-3.3 to -8.6 sd below average)

Clinical features from OMIM®:

618157 (Updated 20-May-2021)

Drugs & Therapeutics for Isolated Growth Hormone Deficiency, Type Iv

Drugs for Isolated Growth Hormone Deficiency, Type Iv (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Hormones

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Pituitary Size and Function in Familial Dwarfism of Sindh Completed NCT00004365

Search NIH Clinical Center for Isolated Growth Hormone Deficiency, Type Iv

Genetic Tests for Isolated Growth Hormone Deficiency, Type Iv

Genetic tests related to Isolated Growth Hormone Deficiency, Type Iv:

# Genetic test Affiliating Genes
1 Isolated Growth Hormone Deficiency, Type 4 29 GHRHR

Anatomical Context for Isolated Growth Hormone Deficiency, Type Iv

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

40
Pituitary, Bone

Publications for Isolated Growth Hormone Deficiency, Type Iv

Articles related to Isolated Growth Hormone Deficiency, Type Iv:

(show all 24)
# Title Authors PMID Year
1
Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults. 6 57
17911170 2007
2
Lack of evidence of premature atherosclerosis in untreated severe isolated growth hormone (GH) deficiency due to a GH-releasing hormone receptor mutation. 6 57
16522693 2006
3
Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient patients with mutated GH-releasing hormone receptor. 6 57
11443201 2001
4
Three new mutations in the gene for the growth hormone (gh)-releasing hormone receptor in familial isolated gh deficiency type ib. 6 57
11232012 2001
5
Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding proteins, and ternary complex formation throughout life. 6 57
10566659 1999
6
Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene. 6 57
10084571 1999
7
Nonsense mutation in the human growth hormone-releasing hormone receptor causes growth failure analogous to the little (lit) mouse. 57 6
8528260 1996
8
Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent advances. 57
24450934 2014
9
Height gain with combined growth hormone and gonadotropin-releasing hormone analog therapy in two pubertal siblings with a growth hormone-releasing hormone receptor mutation. 57
17925337 2008
10
Heterozygosity for a mutation in the growth hormone-releasing hormone receptor gene does not influence adult stature, but affects body composition. 6
17356054 2007
11
Haplotype analysis of the growth hormone releasing hormone receptor locus in three apparently unrelated kindreds from the indian subcontinent with the identical mutation in the GHRH receptor. 6
12794696 2003
12
The Impact of congenital, severe, untreated growth hormone (GH) deficiency on bone size and density in young adults: insights from genetic GH-releasing hormone receptor deficiency. 6
12788864 2003
13
Decreased expression of the GHRH receptor gene due to a mutation in a Pit-1 binding site. 6
11875102 2002
14
Growth hormone deficiency type IB caused by cryptic splicing of the GH-1 gene. 6
10689634 2000
15
Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency. 6
10678654 2000
16
Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh. 6
9814493 1998
17
Extensive phenotypic analysis of a family with growth hormone (GH) deficiency caused by a mutation in the GH-releasing hormone receptor gene. 6
9467553 1998
18
Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency. 57
8288694 1994
19
GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. 57
8395283 1993
20
Molecular basis of the little mouse phenotype and implications for cell type-specific growth. 57
8391647 1993
21
Heterogeneous growth hormone (GH) gene mutations in familial GH deficiency. 6
8496314 1993
22
DSab-origin: a novel IGHD sensitive VDJ mapping method and its application on antibody response after influenza vaccination. 61
30871465 2019
23
Mutational status and gene repertoire of IGHV-IGHD-IGHJ rearrangements in Serbian patients with chronic lymphocytic leukemia. 61
22560084 2012
24
Reconsidering the human immunoglobulin heavy-chain locus: 1. An evaluation of the expressed human IGHD gene repertoire. 61
16402215 2006

Variations for Isolated Growth Hormone Deficiency, Type Iv

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

6 (show top 50) (show all 75)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GH1 , GH-LCR NM_000515.5(GH1):c.456+1G>C SNV Pathogenic 15966 rs797044449 GRCh37: 17:61995119-61995119
GRCh38: 17:63917759-63917759
2 GH1 , GH-LCR NM_000515.5(GH1):c.456+1G>T SNV Pathogenic 15967 rs797044449 GRCh37: 17:61995119-61995119
GRCh38: 17:63917759-63917759
3 GH1 , GH-LCR NM_000515.5(GH1):c.456+5G>C SNV Pathogenic 15976 rs863223308 GRCh37: 17:61995115-61995115
GRCh38: 17:63917755-63917755
4 GHRHR Indel Pathogenic 56966 GRCh37: 7:30999250-31006943
GRCh38: 7:30959635-30967328
5 GHRHR NC_000007.14:g.31008681G>T SNV Pathogenic 626257 rs1562606449 GRCh37: 7:31048296-31048296
GRCh38: 7:31008681-31008681
6 GHRHR NM_000823.4(GHRHR):c.214G>T (p.Glu72Ter) SNV Pathogenic 15989 rs121918117 GRCh37: 7:31008731-31008731
GRCh38: 7:30969116-30969116
7 GHRHR NM_000823.4(GHRHR):c.57+1G>A SNV Pathogenic 15990 rs2302022 GRCh37: 7:31003741-31003741
GRCh38: 7:30964126-30964126
8 GHRHR NM_000823.4(GHRHR):c.431T>A (p.Leu144His) SNV Pathogenic 15991 rs121918118 GRCh37: 7:31010798-31010798
GRCh38: 7:30971183-30971183
9 GHRHR NM_000823.4(GHRHR):c.725T>G (p.Phe242Cys) SNV Pathogenic 15992 rs121918119 GRCh37: 7:31013727-31013727
GRCh38: 7:30974112-30974112
10 GHRHR NM_000823.4(GHRHR):c.665C>A (p.Ala222Glu) SNV Pathogenic 15993 rs121918120 GRCh37: 7:31013667-31013667
GRCh38: 7:30974052-30974052
11 GHRHR NM_000823.4(GHRHR):c.985A>G (p.Lys329Glu) SNV Pathogenic 15994 rs121918121 GRCh37: 7:31016054-31016054
GRCh38: 7:30976439-30976439
12 GHRHR GHRHR, -124A-C, PROMOTER SNV Pathogenic 15995 GRCh37:
GRCh38:
13 GHRHR NM_000823.4(GHRHR):c.1089_1093del (p.Leu364fs) Deletion Pathogenic 265396 rs748432685 GRCh37: 7:31016156-31016160
GRCh38: 7:30976541-30976545
14 GHRHR NM_000823.4(GHRHR):c.967C>T (p.Gln323Ter) SNV Pathogenic 1064692 GRCh37: 7:31015476-31015476
GRCh38: 7:30975861-30975861
15 GHRHR NM_000823.4(GHRHR):c.731G>A (p.Trp244Ter) SNV Likely pathogenic 998031 GRCh37: 7:31013733-31013733
GRCh38: 7:30974118-30974118
16 GHRHR NM_000823.4(GHRHR):c.481C>T (p.Arg161Trp) SNV Likely pathogenic 998042 GRCh37: 7:31011594-31011594
GRCh38: 7:30971979-30971979
17 GHRHR NM_000823.4(GHRHR):c.418T>C (p.Ser140Pro) SNV Likely pathogenic 161435 rs606231412 GRCh37: 7:31010785-31010785
GRCh38: 7:30971170-30971170
18 GHRHR NM_000823.4(GHRHR):c.281G>A (p.Arg94Gln) SNV Likely pathogenic 161436 rs200848306 GRCh37: 7:31009494-31009494
GRCh38: 7:30969879-30969879
19 GHRHR NM_000823.4(GHRHR):c.495C>A (p.His165Gln) SNV Likely pathogenic 161437 rs606231413 GRCh37: 7:31011608-31011608
GRCh38: 7:30971993-30971993
20 GHRHR NM_000823.4(GHRHR):c.1250del (p.Lys417fs) Deletion Conflicting interpretations of pathogenicity 632503 rs771060895 GRCh37: 7:31018835-31018835
GRCh38: 7:30979220-30979220
21 GHRHR NM_000823.4(GHRHR):c.975-6C>A SNV Uncertain significance 729746 rs117572522 GRCh37: 7:31016038-31016038
GRCh38: 7:30976423-30976423
22 GHRHR NM_000823.4(GHRHR):c.489C>T (p.Tyr163=) SNV Uncertain significance 198104 rs147098353 GRCh37: 7:31011602-31011602
GRCh38: 7:30971987-30971987
23 GHRHR NM_000823.4(GHRHR):c.53C>T (p.Pro18Leu) SNV Uncertain significance 1031665 GRCh37: 7:31003736-31003736
GRCh38: 7:30964121-30964121
24 GH1 , GH-LCR NM_000515.5(GH1):c.246G>C (p.Glu82Asp) SNV Uncertain significance 889155 GRCh37: 17:61995422-61995422
GRCh38: 17:63918062-63918062
25 GHRHR NM_000823.4(GHRHR):c.489C>G (p.Tyr163Ter) SNV Uncertain significance 632502 rs147098353 GRCh37: 7:31011602-31011602
GRCh38: 7:30971987-30971987
26 GHRHR NM_000823.4(GHRHR):c.10C>T (p.Arg4Trp) SNV Uncertain significance 909041 GRCh37: 7:31003693-31003693
GRCh38: 7:30964078-30964078
27 GHRHR NM_000823.4(GHRHR):c.47C>T (p.Pro16Leu) SNV Uncertain significance 909042 GRCh37: 7:31003730-31003730
GRCh38: 7:30964115-30964115
28 GHRHR NM_000823.4(GHRHR):c.93C>T (p.Ile31=) SNV Uncertain significance 749584 rs143429066 GRCh37: 7:31008484-31008484
GRCh38: 7:30968869-30968869
29 GHRHR NM_000823.4(GHRHR):c.751+12G>A SNV Uncertain significance 912020 GRCh37: 7:31013765-31013765
GRCh38: 7:30974150-30974150
30 GHRHR NM_000823.4(GHRHR):c.760G>A (p.Val254Met) SNV Uncertain significance 912022 GRCh37: 7:31014052-31014052
GRCh38: 7:30974437-30974437
31 GHRHR NM_000823.4(GHRHR):c.882+11G>A SNV Uncertain significance 912023 GRCh37: 7:31014666-31014666
GRCh38: 7:30975051-30975051
32 GHRHR NM_000823.4(GHRHR):c.512C>G (p.Thr171Ser) SNV Uncertain significance 287138 rs10227922 GRCh37: 7:31011625-31011625
GRCh38: 7:30972010-30972010
33 GHRHR NM_000823.4(GHRHR):c.279A>G (p.Lys93=) SNV Uncertain significance 909904 GRCh37: 7:31009492-31009492
GRCh38: 7:30969877-30969877
34 GHRHR NM_000823.4(GHRHR):c.359C>T (p.Ala120Val) SNV Uncertain significance 909905 GRCh37: 7:31009572-31009572
GRCh38: 7:30969957-30969957
35 GHRHR NM_000823.4(GHRHR):c.447C>T (p.Thr149=) SNV Uncertain significance 909906 GRCh37: 7:31010814-31010814
GRCh38: 7:30971199-30971199
36 GHRHR NM_000823.4(GHRHR):c.*88T>A SNV Uncertain significance 909959 GRCh37: 7:31018947-31018947
GRCh38: 7:30979332-30979332
37 GHRHR NM_000823.4(GHRHR):c.490G>A (p.Val164Ile) SNV Uncertain significance 910805 GRCh37: 7:31011603-31011603
GRCh38: 7:30971988-30971988
38 GHRHR NM_000823.4(GHRHR):c.507C>G (p.Phe169Leu) SNV Uncertain significance 910806 GRCh37: 7:31011620-31011620
GRCh38: 7:30972005-30972005
39 GHRHR NM_000823.4(GHRHR):c.580C>T (p.His194Tyr) SNV Uncertain significance 910807 GRCh37: 7:31011693-31011693
GRCh38: 7:30972078-30972078
40 GHRHR NM_000823.4(GHRHR):c.660G>A (p.Leu220=) SNV Uncertain significance 597235 rs145466944 GRCh37: 7:31013662-31013662
GRCh38: 7:30974047-30974047
41 GHRHR NM_000823.4(GHRHR):c.6C>T (p.Asp2=) SNV Uncertain significance 911972 GRCh37: 7:31003689-31003689
GRCh38: 7:30964074-30964074
42 GHRHR NM_000823.4(GHRHR):c.914G>A (p.Arg305His) SNV Uncertain significance 360036 rs200472991 GRCh37: 7:31015423-31015423
GRCh38: 7:30975808-30975808
43 GHRHR NM_000823.4(GHRHR):c.57+1G>T SNV Uncertain significance 360028 rs2302022 GRCh37: 7:31003741-31003741
GRCh38: 7:30964126-30964126
44 GHRHR NM_000823.4(GHRHR):c.640A>G (p.Met214Val) SNV Uncertain significance 360032 rs535947130 GRCh37: 7:31013642-31013642
GRCh38: 7:30974027-30974027
45 GHRHR NM_000823.4(GHRHR):c.812+12C>T SNV Uncertain significance 360034 rs151020002 GRCh37: 7:31014116-31014116
GRCh38: 7:30974501-30974501
46 GHRHR NM_000823.4(GHRHR):c.*198C>A SNV Uncertain significance 360040 rs886062276 GRCh37: 7:31019057-31019057
GRCh38: 7:30979442-30979442
47 GHRHR NM_000823.4(GHRHR):c.875C>G (p.Ser292Trp) SNV Uncertain significance 360035 rs527387367 GRCh37: 7:31014648-31014648
GRCh38: 7:30975033-30975033
48 GHRHR NM_000823.4(GHRHR):c.*51C>T SNV Uncertain significance 360038 rs185262577 GRCh37: 7:31018910-31018910
GRCh38: 7:30979295-30979295
49 GHRHR NM_000823.4(GHRHR):c.29T>G (p.Val10Gly) SNV Uncertain significance 360027 rs139599160 GRCh37: 7:31003712-31003712
GRCh38: 7:30964097-30964097
50 GHRHR NM_000823.4(GHRHR):c.741C>T (p.Leu247=) SNV Uncertain significance 284569 rs151019928 GRCh37: 7:31013743-31013743
GRCh38: 7:30974128-30974128

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

72
# Symbol AA change Variation ID SNP ID
1 GHRHR p.Leu144His VAR_015796 rs121918118
2 GHRHR p.Ala176Val VAR_015797 rs774281185
3 GHRHR p.Ala222Glu VAR_015798 rs121918120
4 GHRHR p.Phe242Cys VAR_015799 rs121918119
5 GHRHR p.Lys329Glu VAR_015800 rs121918121

Expression for Isolated Growth Hormone Deficiency, Type Iv

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

Pathways for Isolated Growth Hormone Deficiency, Type Iv

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.21 GHRHR GH1

GO Terms for Isolated Growth Hormone Deficiency, Type Iv

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

# Name GO ID Score Top Affiliating Genes
1 positive regulation of multicellular organism growth GO:0040018 8.96 GHRHR GH1
2 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 8.62 GHRHR GH1

Sources for Isolated Growth Hormone Deficiency, Type Iv

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....