The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter

Ambrosio, Raffaele; Fimiani, Giorgia; Monfregola, Jlenia; Sanzari, Emma; Felice, Nicola De; Salerno, Maria Carolina; Pignata, Claudio; D’Urso, Michele; Ursini, Matilde Valeria

doi:10.1016/s0378-1119(02)00421-3

Cited by 46 publications

(34 citation statements)

References 28 publications

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“…Ambrosio et al (18) evaluated STAT5b as a candidate gene in children with 'idiopathic short stature,' but no base alterations were observed other than two polymorphisms. A recent report, however, of a 16-year-old girl from consanguineous Argentine parents, associated severe postnatal growth failure (height 2 7.5 S.D.…”

Section: Gh Insensitivity Resulting From Defects Of Gh Signalingmentioning

confidence: 99%

New molecular mechanisms of GH resistance

Rosenfeld

Hwa

2004

European Journal of Endocrinology

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Primary growth hormone (GH) resistance describes growth failure in the presence of normal, or even elevated, GH secretion. In its classic form, the phenotype is identical to that of GH deficiency, and was originally described in association with defects of the GH receptor. With increasing understanding of the GH -insulin-like growth factor (IGF) axis, it has become apparent that GH resistance can result from either primary IGF deficiency (IGFD) or IGF resistance. Primary IGFD may be due to: (i) defects of the GH receptor, (ii) defects of post-GH receptor signaling or (iii) primary defects of IGF-I synthesis. IGF resistance may result from: (i) defects of the IGF receptor, (ii) defects of post-IGF receptor signaling, (iii) defects of IGF binding proteins or (iv) defects of the epiphyseal growth plate or of regulatory proteins involved in epiphyseal growth.European Journal of Endocrinology 151 S11-S15

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Section: Gh Insensitivity Resulting From Defects Of Gh Signalingmentioning

confidence: 99%

New molecular mechanisms of GH resistance

Rosenfeld

Hwa

2004

European Journal of Endocrinology

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“…Exon 13 of the STAT5b gene encodes part of the Linker domain in the STAT5b protein [17]. The STAT family of proteins (fig.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone Insensitivity and Severe Short Stature in Siblings: A Novel Mutation at the Exon 13-Intron 13 Junction of the <i>STAT5b</i> Gene

et al. 2007

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Background/Aims: Growth hormone insensitivity (GHI) is characterized by severe short stature, high serum growth hormone (GH), low serum IGF-I and IGFBP-3 levels and is classically associated with genetic defects of the GH receptor (GHR). Recently, mutations of the STAT5b gene have been identified and shown to be associated with GHI and severe IGF deficiency. We investigated 2 sisters from a consanguineous family from Kuwait, with clinical and biochemical features of GHI, in whom no molecular defects in the GHR were identified. Methods: Serum and DNA were analyzed. Results: In addition to GHI, siblings 2 and 1 presented with, respectively, a diagnosis of juvenile idiopathic arthritis and recurrent pulmonary infections. Molecular analysis of the STAT5b gene revealed a novel homozygous deletion of a G at the junction of exon 13-intron 13. The parents, who are of normal height, were heterozygous for the mutation. Conclusions: This is the first STAT5b defect to be identified in siblings, further supporting the autosomal recessive mode of transmission of STAT5b deficiency. The results affirm that defective STAT5b is an etiology for IGF deficiency and the GHI phenotype, and emphasize the importance of considering this diagnosis in patients with IGF deficiency, especially when associated with diverse immunological problems.

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“…In accordance with these results, the quantitative TCR rearrangement PCR of the PB MNC fraction showed an abnormal T-cell expansion (supplemental Figure 2). As STAT5a and STAT5b protein structures are very similar, and they are capable of homo-and heterodimerization with each other, 15,16 we next designed amplicon sequencing primers to cover exon 17 of STAT5a, corresponding to the exon 16 of STAT5b. Adjacent exons (15-16 and 18-19) were sequenced by capillary sequencing.…”

Section: Cd56mentioning

confidence: 99%

Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia

Rajala

Eldfors

Kuusanmäki

et al. 2013

Blood

257

234

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• Somatic mutations were discovered for the first time in the SH2 domain of the STAT5b gene in LGL leukemia.• The mutations are activating and lead to increased phosphorylation and transcriptional activity of STAT5b.Large granular lymphocytic (LGL) leukemia is characterized by clonal expansion of cytotoxic T cells or natural killer cells. Recently, somatic mutations in the signal transducer and activator of transcription 3 (STAT3) gene were discovered in 28% to 40% of LGL leukemia patients. By exome and transcriptome sequencing of 2 STAT3 mutation-negative LGL leukemia patients, we identified a recurrent, somatic missense mutation (Y665F) in the Srclike homology 2 domain of the STAT5b gene. Targeted amplicon sequencing of 211 LGL leukemia patients revealed 2 additional patients with STAT5b mutations (N642H), resulting in a total frequency of 2% (4 of 211) of STAT5b mutations across all patients. The Y665F and N642H mutant constructs increased the transcriptional activity of STAT5 and tyrosine (Y694) phosphorylation, which was also observed in patient samples. The clinical course of the disease in patients with the N642H mutation was aggressive and fatal, clearly different from typical LGL leukemia with a relatively favorable outcome. This is the first time somatic STAT5 mutations are discovered in human cancer and further emphasizes the role of STAT family genes in the pathogenesis of LGL leukemia. (Blood. 2013;121(22):4541-4550)

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The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter

Cited by 46 publications

References 28 publications

New molecular mechanisms of GH resistance

New molecular mechanisms of GH resistance

Growth Hormone Insensitivity and Severe Short Stature in Siblings: A Novel Mutation at the Exon 13-Intron 13 Junction of the <i>STAT5b</i> Gene

Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia

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