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9 záznamů v Medvik Filtry

Článek

Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: Frequencies, phenotypes and growth outcomes

Blum, Werner F
Autor Blum, Werner F University Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany Center of Child and Adolescent Medicine, Justus Liebig University, Feulgenstrasse 12, 35392 Giessen, Germany. Electronic address: wernblum@gmail.com
Klammt, Jürgen
Autor Klammt, Jürgen University Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany
Amselem, Serge
Autor Amselem, Serge Sorbonne Université, Inserm UMR_S933, Département de Génétique, Hôpital Trousseau, AP-HP, 75012 Paris, France
Pfäffle, Heike M
Autor Pfäffle, Heike M University Hospital for Children and Adolescents, University of Leipzig, Liebigstrasse 20a, 04103 Leipzig, Germany
Legendre, Marie
Autor Legendre, Marie Sorbonne Université, Inserm UMR_S933, Département de Génétique, Hôpital Trousseau, AP-HP, 75012 Paris, France
Sobrier, Marie-Laure
Autor Sobrier, Marie-Laure Sorbonne Université, Inserm UMR_S933, Département de Génétique, Hôpital Trousseau, AP-HP, 75012 Paris, France
Luton, Marie-Pierre
Autor Luton, Marie-Pierre Sorbonne Université, Inserm UMR_S933, Département de Génétique, Hôpital Trousseau, AP-HP, 75012 Paris, France
Child, Christopher J
Autor Child, Christopher J Eli Lilly and Company, Windlesham, GU20 6PH, UK
Jones, Christine
Autor Jones, Christine Eli Lilly and Company, Werner-Reimers-Strasse 2-4, 61352 Bad Homburg, Germany
Zimmermann, Alan G
Autor Zimmermann, Alan G Eli Lilly and Company, Indianapolis, USA

EBioMedicine. 2018 ; 36 (-) : 390-400. [pub] 20180925

ISSN 2352-3964
Medvik
Zdroj

Článek

Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation

Nature communications. 2018 ; 9 (1) : 2105. [pub] 20180529

Nat Commun
ISSN 2041-1723
Medvik
Zdroj

Growth hormone (GH) insensitivity syndrome (GHIS) is a rare clinical condition in which production of insulin-like growth factor 1 is blunted and, consequently, postnatal growth impaired. Autosomal-recessive mutations in signal transducer and activator of transcription (STAT5B), the key signal transducer for GH, cause severe GHIS with additional characteristics of immune and, often fatal, pulmonary complications. Here we report dominant-negative, inactivating STAT5B germline mutations in patients with growth failure, eczema, and elevated IgE but without severe immune and pulmonary problems. These STAT5B missense mutants are robustly tyrosine phosphorylated upon stimulation, but are unable to nuclear localize, or fail to bind canonical STAT5B DNA response elements. Importantly, each variant retains the ability to dimerize with wild-type STAT5B, disrupting the normal transcriptional functions of wild-type STAT5B. We conclude that these STAT5B variants exert dominant-negative effects through distinct pathomechanisms, manifesting in milder clinical GHIS with general sparing of the immune system.