Growth Hormone Insensitivity with Immunodeficiency

Categories: Endocrine diseases, Immune diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Growth Hormone Insensitivity with Immunodeficiency

MalaCards integrated aliases for Growth Hormone Insensitivity with Immunodeficiency:

Name: Growth Hormone Insensitivity with Immunodeficiency 20 36 6 39
Growth Hormone Insensitivity Due to Postreceptor Defect 20
Laron Syndrome Due to Postreceptor Defect 20


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KEGG 36 H00931

Summaries for Growth Hormone Insensitivity with Immunodeficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 181393 Definition 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). Epidemiology A few cases of IGF-1 deficiency, IGF-1 resistance, STAT5B and ALS deficiencies, and more than 250 cases of Laron syndrome have been reported in the literature so far. Males and females are equally affected. Clinical description Intrauterine growth and birth size are usually subnormal. Postnatal growth is slowed. Facial dysmorphism is common and includes microcephaly, thin upper and everted lower lips and small chin. Disproportional growth, delayed motor development and delayed puberty have been described in some cases and relative obesity may occur in young adults. Intellectual development varies from normal intelligence to intellectual deficiency. Despite sharing short stature and the classical biochemical features of GH insensitivity, affected individuals present heterogeneous clinical features depending on the genetic condition. Immune deficiency has been described in some cases of STAT5b deficiency. Hearing loss has been described in some cases of IGF-1 deficiency. Etiology GHIS is due to mutations in the growth hormone receptor ( GHR ) gene (Laron syndrome) or to post receptor defects due to mutations in the IGF-1 (IGF-1 deficiency and IGF-1 resistance), IGFALS (short stature due to primary ALS deficiency) or STAT5B genes (STAT5b deficiency). Transmission is autosomal recessive. Diagnostic methods The diagnosis is based on clinical and biological findings. Hormonal tests reveal normal or high serum concentrations of GH. IGF-1 and growth hormone binding protein (GHBP) levels depend on the disease-causing mutations. IGF-1 levels are low in cases ofGHR defects, STAT5b, IGF-1 and ALS deficiencies, and high in cases of IGF-1 resistance. GHBP levels are low in cases of mutations in the extracellular domain of GHR and normal in cases of mutations in the intracellular domain of GHR or post receptor defects. IGF-BP 3 levels are low in cases of GHR, STAT5b, and ALS deficiencies, normal in cases of IGF-1 deficiency. ALS levels are low in cases of ALS deficiencies. Genetic tests should be performed to make a precise etiological diagnosis. Differential diagnosis The differential diagnosis should include secondary IGF-1 deficiency due to nutritional problems or chronic pediatric diseases. Genetic counseling Genetic counseling should be proposed to parents of an affected individual before any further pregnancy, informing them of the risks and the available diagnostic methods. Management and treatment Management aims at improving growth and, except for IGF-1 resistance, includes treatment with daily subcutaneous injections of mecasermin, a recombinant human IGF-1, and diet with adequate caloric intake. In August 2005, mecasermin was granted EC orphan drug designation. Growth hormone treatment may partially improve growth in cases of IGF-1 resistance. There is no treatment that cures or prevents the disease. Prognosis With age, osteoporosis can become apparent. Patients may develop obesity, hypercholesterolemia, insulin resistance, glucose intolerance and even type II diabetes.

MalaCards based summary : Growth Hormone Insensitivity with Immunodeficiency, also known as growth hormone insensitivity due to postreceptor defect, is related to growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive. An important gene associated with Growth Hormone Insensitivity with Immunodeficiency is STAT5B (Signal Transducer And Activator Of Transcription 5B), and among its related pathways/superpathways are ErbB signaling pathway and Chemokine signaling pathway.

KEGG : 36 Growth hormone insensitivity with immunodeficiency is a combined phenotype of growth hormone insensitivity that resembles Laron syndrome and immunodeficiency. Homozygous inactivating mutation in the STAT5b, a component of the GH signaling pathway, leads to a complete absence of protein expression.

Related Diseases for Growth Hormone Insensitivity with Immunodeficiency

Diseases related to Growth Hormone Insensitivity with Immunodeficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 growth hormone insensitivity syndrome with immune dysregulation 1, autosomal recessive 11.7

Symptoms & Phenotypes for Growth Hormone Insensitivity with Immunodeficiency

Drugs & Therapeutics for Growth Hormone Insensitivity with Immunodeficiency

Search Clinical Trials , NIH Clinical Center for Growth Hormone Insensitivity with Immunodeficiency

Genetic Tests for Growth Hormone Insensitivity with Immunodeficiency

Anatomical Context for Growth Hormone Insensitivity with Immunodeficiency

Publications for Growth Hormone Insensitivity with Immunodeficiency

Articles related to Growth Hormone Insensitivity with Immunodeficiency:

# Title Authors PMID Year
STAT5B deficiency: Impacts on human growth and immunity. 6
26703237 2016
Characterization of immunodeficiency in a patient with growth hormone insensitivity secondary to a novel STAT5b gene mutation. 6
17030597 2006
Clinical and biochemical characteristics of a male patient with a novel homozygous STAT5b mutation. 6
16787985 2006
A mutant signal transducer and activator of transcription 5b, associated with growth hormone insensitivity and insulin-like growth factor-I deficiency, cannot function as a signal transducer or transcription factor. 6
16464942 2006
Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. 6
15827093 2005
Growth hormone insensitivity associated with a STAT5b mutation. 6
13679528 2003

Variations for Growth Hormone Insensitivity with Immunodeficiency

ClinVar genetic disease variations for Growth Hormone Insensitivity with Immunodeficiency:

6 (show top 50) (show all 101)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 STAT5B NM_012448.3(STAT5B):c.1888G>C (p.Ala630Pro) SNV Pathogenic 5694 rs121908501 GRCh37: 17:40362207-40362207
GRCh38: 17:42210189-42210189
2 STAT5B STAT5B, 1-BP INS, 1191G Insertion Pathogenic 5695 GRCh37:
3 STAT5B NM_012448.3(STAT5B):c.454C>T (p.Arg152Ter) SNV Pathogenic 5697 rs121908502 GRCh37: 17:40375496-40375496
GRCh38: 17:42223478-42223478
4 STAT5B STAT5B, 1-BP DEL, EXON 13/INTRON 13 JUNCTION Deletion Pathogenic 5698 GRCh37:
5 STAT5B NM_012448.3(STAT5B):c.1421A>G (p.Gln474Arg) SNV Pathogenic 492931 rs1555548680 GRCh37: 17:40368084-40368084
GRCh38: 17:42216066-42216066
6 STAT5B NM_012448.3(STAT5B):c.1433C>T (p.Ala478Val) SNV Pathogenic 517661 rs1555548678 GRCh37: 17:40368072-40368072
GRCh38: 17:42216054-42216054
7 STAT5B NM_012448.3(STAT5B):c.530A>C (p.Gln177Pro) SNV Pathogenic 522611 rs1555549674 GRCh37: 17:40375420-40375420
GRCh38: 17:42223402-42223402
8 STAT5B NM_012448.3(STAT5B):c.1102dup (p.Gln368fs) Duplication Pathogenic 579749 rs761761205 GRCh37: 17:40370235-40370236
GRCh38: 17:42218217-42218218
9 STAT5B NM_012448.4(STAT5B):c.1102del (p.Gln368fs) Deletion Pathogenic 840661 GRCh37: 17:40370236-40370236
GRCh38: 17:42218218-42218218
10 STAT5B NM_012448.3(STAT5B):c.1924A>C (p.Asn642His) SNV Conflicting interpretations of pathogenicity 657518 rs938448224 GRCh37: 17:40359729-40359729
GRCh38: 17:42207711-42207711
11 STAT5B NM_012448.3(STAT5B):c.551-5T>C SNV Conflicting interpretations of pathogenicity 534583 rs200299299 GRCh37: 17:40371865-40371865
GRCh38: 17:42219847-42219847
12 STAT5B NM_012448.3(STAT5B):c.2065G>A (p.Glu689Lys) SNV Uncertain significance 570083 rs778995803 GRCh37: 17:40359588-40359588
GRCh38: 17:42207570-42207570
13 STAT5B NM_012448.3(STAT5B):c.2018G>A (p.Arg673Gln) SNV Uncertain significance 575338 rs776285574 GRCh37: 17:40359635-40359635
GRCh38: 17:42207617-42207617
14 STAT5B NM_012448.3(STAT5B):c.773G>A (p.Arg258Gln) SNV Uncertain significance 578442 rs1314726288 GRCh37: 17:40371390-40371390
GRCh38: 17:42219372-42219372
15 STAT5B NM_012448.3(STAT5B):c.1596C>A (p.Phe532Leu) SNV Uncertain significance 466222 rs1555548243 GRCh37: 17:40364086-40364086
GRCh38: 17:42212068-42212068
16 STAT5B NM_012448.3(STAT5B):c.319C>T (p.Arg107Cys) SNV Uncertain significance 534576 rs1177773526 GRCh37: 17:40376853-40376853
GRCh38: 17:42224835-42224835
17 STAT5B NM_012448.3(STAT5B):c.1408G>A (p.Val470Ile) SNV Uncertain significance 534577 rs1555548681 GRCh37: 17:40368097-40368097
GRCh38: 17:42216079-42216079
18 STAT5B NM_012448.3(STAT5B):c.691G>A (p.Glu231Lys) SNV Uncertain significance 534578 rs917567542 GRCh37: 17:40371472-40371472
GRCh38: 17:42219454-42219454
19 STAT5B NM_012448.3(STAT5B):c.787G>A (p.Gly263Arg) SNV Uncertain significance 640215 rs759281260 GRCh37: 17:40371376-40371376
GRCh38: 17:42219358-42219358
20 STAT5B NM_012448.3(STAT5B):c.2005G>A (p.Val669Met) SNV Uncertain significance 645841 rs1339796170 GRCh37: 17:40359648-40359648
GRCh38: 17:42207630-42207630
21 STAT5B NM_012448.3(STAT5B):c.1337C>T (p.Ser446Phe) SNV Uncertain significance 645970 rs1598301960 GRCh37: 17:40369221-40369221
GRCh38: 17:42217203-42217203
22 STAT5B NM_012448.3(STAT5B):c.550+5G>A SNV Uncertain significance 648019 rs773246323 GRCh37: 17:40375395-40375395
GRCh38: 17:42223377-42223377
23 STAT5B NM_012448.3(STAT5B):c.1346G>A (p.Ser449Asn) SNV Uncertain significance 649182 rs1598301952 GRCh37: 17:40369212-40369212
GRCh38: 17:42217194-42217194
24 STAT5B NM_012448.3(STAT5B):c.2176A>G (p.Met726Val) SNV Uncertain significance 649575 rs1598292098 GRCh37: 17:40354419-40354419
GRCh38: 17:42202401-42202401
25 STAT5B NM_012448.3(STAT5B):c.2098G>T (p.Val700Leu) SNV Uncertain significance 657964 rs1567653213 GRCh37: 17:40354806-40354806
GRCh38: 17:42202788-42202788
26 STAT5B NM_012448.3(STAT5B):c.440C>T (p.Thr147Met) SNV Uncertain significance 658036 rs768919211 GRCh37: 17:40375510-40375510
GRCh38: 17:42223492-42223492
27 STAT5B NM_012448.3(STAT5B):c.1084G>A (p.Val362Met) SNV Uncertain significance 660268 rs750053820 GRCh37: 17:40370254-40370254
GRCh38: 17:42218236-42218236
28 STAT5B NM_012448.4(STAT5B):c.703A>C (p.Lys235Gln) SNV Uncertain significance 1034435 GRCh37: 17:40371460-40371460
GRCh38: 17:42219442-42219442
29 STAT5B NM_012448.4(STAT5B):c.2359T>C (p.Ser787Pro) SNV Uncertain significance 1037184 GRCh37: 17:40353761-40353761
GRCh38: 17:42201743-42201743
30 STAT5B NM_012448.4(STAT5B):c.638C>G (p.Ala213Gly) SNV Uncertain significance 1039656 GRCh37: 17:40371773-40371773
GRCh38: 17:42219755-42219755
31 STAT5B NM_012448.4(STAT5B):c.7G>A (p.Val3Met) SNV Uncertain significance 1040866 GRCh37: 17:40384139-40384139
GRCh38: 17:42232121-42232121
32 STAT5B NM_012448.3(STAT5B):c.1591G>A (p.Val531Met) SNV Uncertain significance 534575 rs142918872 GRCh37: 17:40364091-40364091
GRCh38: 17:42212073-42212073
33 STAT5B NM_012448.4(STAT5B):c.91C>T (p.Arg31Trp) SNV Uncertain significance 975961 GRCh37: 17:40384055-40384055
GRCh38: 17:42232037-42232037
34 STAT5B NM_012448.4(STAT5B):c.550+7C>T SNV Uncertain significance 828010 rs771507023 GRCh37: 17:40375393-40375393
GRCh38: 17:42223375-42223375
35 STAT5B NM_012448.4(STAT5B):c.925G>C (p.Val309Leu) SNV Uncertain significance 836252 GRCh37: 17:40370805-40370805
GRCh38: 17:42218787-42218787
36 STAT5B NM_012448.4(STAT5B):c.2348C>T (p.Pro783Leu) SNV Uncertain significance 848018 GRCh37: 17:40353772-40353772
GRCh38: 17:42201754-42201754
37 STAT5B NM_012448.4(STAT5B):c.539T>A (p.Leu180Gln) SNV Uncertain significance 851703 GRCh37: 17:40375411-40375411
GRCh38: 17:42223393-42223393
38 STAT5B NM_012448.4(STAT5B):c.2215C>T (p.His739Tyr) SNV Uncertain significance 842829 GRCh37: 17:40354380-40354380
GRCh38: 17:42202362-42202362
39 STAT5B NM_012448.4(STAT5B):c.13A>T (p.Ile5Leu) SNV Uncertain significance 934489 GRCh37: 17:40384133-40384133
GRCh38: 17:42232115-42232115
40 STAT5B NM_012448.4(STAT5B):c.1307C>T (p.Thr436Ile) SNV Uncertain significance 936221 GRCh37: 17:40369251-40369251
GRCh38: 17:42217233-42217233
41 STAT5B NM_012448.4(STAT5B):c.178C>T (p.Leu60Phe) SNV Uncertain significance 936890 GRCh37: 17:40379654-40379654
GRCh38: 17:42227636-42227636
42 STAT5B NM_012448.4(STAT5B):c.1619A>G (p.Asn540Ser) SNV Uncertain significance 970790 GRCh37: 17:40364063-40364063
GRCh38: 17:42212045-42212045
43 STAT5B NM_012448.4(STAT5B):c.2293G>A (p.Val765Ile) SNV Uncertain significance 998972 GRCh37: 17:40353827-40353827
GRCh38: 17:42201809-42201809
44 STAT5B NM_012448.4(STAT5B):c.1775+3G>A SNV Uncertain significance 1000937 GRCh37: 17:40362418-40362418
GRCh38: 17:42210400-42210400
45 STAT5B NM_012448.4(STAT5B):c.354G>T (p.Arg118Ser) SNV Uncertain significance 1006767 GRCh37: 17:40376818-40376818
GRCh38: 17:42224800-42224800
46 STAT5B NM_012448.3(STAT5B):c.2167G>A (p.Ala723Thr) SNV Uncertain significance 665889 rs929910807 GRCh37: 17:40354428-40354428
GRCh38: 17:42202410-42202410
47 STAT5B NM_012448.4(STAT5B):c.1117A>G (p.Ile373Val) SNV Uncertain significance 848352 GRCh37: 17:40370221-40370221
GRCh38: 17:42218203-42218203
48 STAT5B NM_012448.4(STAT5B):c.1218C>A (p.His406Gln) SNV Uncertain significance 856714 GRCh37: 17:40369434-40369434
GRCh38: 17:42217416-42217416
49 STAT5B NM_012448.4(STAT5B):c.1845C>G (p.Phe615Leu) SNV Uncertain significance 952309 GRCh37: 17:40362250-40362250
GRCh38: 17:42210232-42210232
50 STAT5B NM_012448.4(STAT5B):c.298C>T (p.Arg100Cys) SNV Uncertain significance 973672 GRCh37: 17:40376874-40376874
GRCh38: 17:42224856-42224856

Expression for Growth Hormone Insensitivity with Immunodeficiency

Search GEO for disease gene expression data for Growth Hormone Insensitivity with Immunodeficiency.

Pathways for Growth Hormone Insensitivity with Immunodeficiency

Pathways related to Growth Hormone Insensitivity with Immunodeficiency according to KEGG:

# Name Kegg Source Accession
1 ErbB signaling pathway hsa04012
2 Chemokine signaling pathway hsa04062
3 JAK-STAT signaling pathway hsa04630

GO Terms for Growth Hormone Insensitivity with Immunodeficiency

Sources for Growth Hormone Insensitivity with Immunodeficiency

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
69 Tocris
71 UMLS via Orphanet
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