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Reviews in Endocrine and Metabolic Disorders

Erschienen in:

08.10.2020

Genetic causes of growth hormone insensitivity beyond GHR

verfasst von: Vivian Hwa, Masanobu Fujimoto, Gaohui Zhu, Wen Gao, Corinne Foley, Meenasri Kumbaji, Ron G. Rosenfeld

Erschienen in: Reviews in Endocrine and Metabolic Disorders | Ausgabe 1/2021

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Abstract

Growth hormone insensitivity (GHI) syndrome, first described in 1966, is classically associated with monogenic defects in the GH receptor (GHR) gene which result in severe post-natal growth failure as consequences of insulin-like growth factor I (IGF-I) deficiency. Over the years, recognition of other monogenic defects downstream of GHR has greatly expanded understanding of primary causes of GHI and growth retardation, with either IGF-I deficiency or IGF-I insensitivity as clinical outcomes. Mutations in IGF1 and signaling component STAT5B disrupt IGF-I production, while defects in IGFALS and PAPPA2, disrupt transport and release of circulating IGF-I, respectively, affecting bioavailability of the growth-promoting IGF-I. Defects in IGF1R, cognate cell-surface receptor for IGF-I, disrupt not only IGF-I actions, but actions of the related IGF-II peptides. The importance of IGF-II for normal developmental growth is emphasized with recent identification of defects in the maternally imprinted IGF2 gene. Current application of next-generation genomic sequencing has expedited the pace of identifying new molecular defects in known genes or in new genes, thereby expanding the spectrum of GH and IGF insensitivity. This review discusses insights gained and future directions from patient-based molecular and functional studies.

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Titel: Genetic causes of growth hormone insensitivity beyond GHR
verfasst von: Vivian Hwa
Masanobu Fujimoto
Gaohui Zhu
Wen Gao
Corinne Foley
Meenasri Kumbaji
Ron G. Rosenfeld
Publikationsdatum: 08.10.2020
Verlag: Springer US
Erschienen in: Reviews in Endocrine and Metabolic Disorders / Ausgabe 1/2021
Print ISSN: 1389-9155
Elektronische ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-020-09603-3

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