Short Stature in a Boy with Multiple Early-Onset Autoimmune Conditions due to a STAT3 Activating Mutation: Could Intracellular Growth Hormone Signalling Be Compromised?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F17%3A10373657" target="_blank" >RIV/00064203:_____/17:10373657 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11130/17:10373657

Result on the web

<a href="https://doi.org/10.1159/000456544" target="_blank" >https://doi.org/10.1159/000456544</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000456544" target="_blank" >10.1159/000456544</a>

Result language

angličtina

Original language name

Short Stature in a Boy with Multiple Early-Onset Autoimmune Conditions due to a STAT3 Activating Mutation: Could Intracellular Growth Hormone Signalling Be Compromised?

Original language description

Background: Germline STAT3 gain-of-function (GOF) mutations cause multiple endocrine and haematologic autoimmune disorders, lymphoproliferation, and growth impairment. As the JAK-STAT pathway is known to transduce the growth hormone (GH) signalling, and STAT3 interacts with STAT5 in growth regulation, we hypothesised that short stature in STAT3 GOF mutations results mostly from GH insensitivity via involving activation of STAT5. Case Report: A boy with a novel STAT3 c.2144C&gt;T (p.Pro715Leu) mutation presented with short stature (-2.60 SD at 5.5 years). He developed diabetes mellitus at 11 months, generalised lymphoproliferation, autoimmune thyroid disease, and immune bicytopenia in the subsequent years. At 5.5 years, his insulin-like growth factor-1 (IGF-I) was 37 mu g/L (-2.22 SD) but stimulated GH was 27.7 mu g/L. Both a standard IGF-I generation test (GH 0.033 mg/kg/day sc; 4 days) and a high-dose prolonged IGF-I generation test (GH 0.067 mg/kg/day sc; 14 days) failed to significantly increase IGF-I levels (37-46 and 72-87 mu g/L, respectively). The boy underwent haematopoietic stem cell transplantation at 6 years due to severe neutropenia and massive lymphoproliferation, but unfortunately deceased 42 days after transplantation from reactivated generalised adenoviral infection. Conclusions: Our findings confirm the effect of STAT3 GOF mutation on the downstream activation of STAT5 resulting in partial GH insensitivity. (C) 2017 S. Karger AG, Basel

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30209 - Paediatrics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Hormone Research in Paediatrics

ISSN

1663-2818

e-ISSN

—

Volume of the periodical

88

Issue of the periodical within the volume

2

Country of publishing house

CH - SWITZERLAND

Number of pages

7

Pages from-to

160-166

UT code for WoS article

000411496600006

EID of the result in the Scopus database

2-s2.0-85029743807