Signal transducer and activator of transcription 5B deficiency due to a novel missense mutation in the coiled-coil domain

Acres, Meghan; Gothe, Florian; Grainger, Angela; Skelton, Andrew; Swan, David J.; Willet, Joseph D. P.; Leech, Suzy; Galcheva, Sonya; Iotova, Violeta; Hambleton, Sophie; Engelhardt, Karin R.

doi:10.1016/j.jaci.2018.08.032

Cited by 15 publications

(19 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of these cases had growth failure secondary to GHI and immunodeficiency due to defects in regulatory T (Treg) cells. Eczema, thrombocytopenic purpura, and/or autoimmune disease like juvenile idiopathic arthritis, autoimmune thyroiditis or celiac disease were present in almost all cases (2)(3)(4). Severe pulmonary disease presenting in early childhood was characteristic feature of most of the cases except in 1 case (5).…”

Section: Discussionmentioning

confidence: 99%

Interstitial lung disease in an adolescent child associated with a novel STAT5B mutation-a case report

Gupta

Mandal

Jat

et al. 2021

Preprint

View full text Add to dashboard Cite

STAT5B protein is an important component of signalling pathway for growth hormone and IL-2 mediated responses. Mutation in STAT5B gene has been reported to be associated with growth hormone insensitivity, immunodeficiency and autoimmunity. Chronic pulmonary involvement is also one component of the disorder. We describe a case an adolescent girl who suffered with poor growth and loose stools since 1 year of age and was subsequently diagnosed with celiac disease and hypothyroidism. She developed features of interstitial lung disease (ILD) which were progressively worsening. Common causes of ILD were ruled out on investigations. She underwent whole exome sequencing and found to be positive for a novel mutation in STAT5B gene on exon 16. On further evaluation, she had growth hormone insensitivity and CD8 cell deficiency. This case highlights that in a child with chronic pulmonary involvement with features suggestive of growth hormone insensitivity, immunodeficiency and autoimmunity, evaluation for STAT5B mutation should be thought of.

show abstract

Section: Discussionmentioning

confidence: 99%

Interstitial lung disease in an adolescent child associated with a novel STAT5B mutation-a case report

Gupta

Mandal

Jat

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Fourteen different mutations in STAT5B (missense, non-sense, deletions, and frameshifts) have been identified so far (12,26,(70)(71)(72)(73). The majority of these involve the Coiled-coiled domain-which is important for protein-protein interactions and nuclear import (74)-, the DNA-binding and the Src homology 2 (SH2) domains, located right upstream of the essential Y699.…”

Section: Stat5b Deficiencymentioning

confidence: 99%

“…Growth failure is the cardinal feature of AR-STAT5B and usually develops after birth, resulting in severe short stature (height ranging from −4.7 to −9.9 Standard Deviation Score, SDS). Delayed bone age and delayed puberty were also noted in some cases (12,(79)(80)(81)(82). Typically, hormonal tests show a phenotype of GH insensitivity (i.e., normal levels of GH and GH-Binding Protein, low levels of IGF-1, IGFBP-3 and Acid Labile Subunit) ( 79), while prolactin levels may be elevated (83,84).…”

Section: Autosomal-recessive Stat5b Deficiencymentioning

confidence: 99%

“…Typically, hormonal tests show a phenotype of GH insensitivity (i.e., normal levels of GH and GH-Binding Protein, low levels of IGF-1, IGFBP-3 and Acid Labile Subunit) ( 79), while prolactin levels may be elevated (83,84). GH-therapy trials were undertaken in some cases but always proved to be ineffective (12,79,81,83).…”

Section: Autosomal-recessive Stat5b Deficiencymentioning

confidence: 99%

“…More recently, similar clinical phenotypes with a wild-type FOXP3 have been identified and subsequently named "IPEX-like disorders" (5). The genetic defect behind these diseases may involve several immunological pathways, such as cell-contact dependent suppression (e.g., CTLA4 haploinsufficiency, LRBA deficiency) (6, 7), JAK-STAT signaling (e.g., STAT1 and STAT3 Gainof-function) (8)(9)(10)(11), or homeostasis, fitness, and maintenance of Treg cells (CD25 and STAT5B deficiencies) (5,12).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

IL-2 Signaling Axis Defects: How Many Faces?

2021

View full text Add to dashboard Cite

CD25, Signal transducer and activator of transcription 5B (STAT5B) and Forkhead box P3 (FOXP3) are critical mediators of Interleukin-2 (IL-2) signaling pathway in regulatory T cells (Tregs). CD25 (i.e., IL-2 Receptor α) binds with high affinity to IL-2, activating STAT5B-mediated signaling that eventually results in transcription of FOXP3, a master regulator of Treg function. Consequently, loss-of-function mutations in these proteins give rise to Treg disorders (i.e., Tregopathies) that clinically result in multiorgan autoimmunity. Immunodysregulation, Polyendocrinopathy Enteropathy X-linked (IPEX), due to mutations in FOXP3, has historically been the prototype of Tregopathies. This review describes current knowledge about defects in CD25, STAT5B, and FOXP3, highlighting that these disorders both share a common biological background and display comparable clinical features. However, specific phenotypes are associated with each of these syndromes, while certain laboratory findings could be helpful tools for clinicians, in order to achieve a prompt genetic diagnosis. Current treatment strategies will be outlined, keeping an eye on gene editing, an interesting therapeutic perspective that could definitely change the natural history of these disorders.

show abstract

Cytopenia in autosomal dominant polycystic kidney disease (ADPKD): merely an association or a disease-related feature with prognostic implications?

et al. 2021

View full text Add to dashboard Cite

Signal transducer and activator of transcription 5B deficiency due to a novel missense mutation in the coiled-coil domain

Cited by 15 publications

References 14 publications

Interstitial lung disease in an adolescent child associated with a novel STAT5B mutation-a case report

Interstitial lung disease in an adolescent child associated with a novel STAT5B mutation-a case report

IL-2 Signaling Axis Defects: How Many Faces?

Cytopenia in autosomal dominant polycystic kidney disease (ADPKD): merely an association or a disease-related feature with prognostic implications?

Contact Info

Product

Resources

About